Autophagy not only plays an important role in the progression of cancer but also is involved in tissue inflammatory response. However, few published studies have investigated associations between functional genetic variants of autophagy-related genes and radiation pneumonitis (RP) as well as clinical outcomes in patients with non-small cell lung cancer (NSCLC) after definitive radiotherapy.We genotyped nine potentially functional single nucleotide polymorphisms (SNPs) in four autophagy-related genes (ATG2B, ATG10, ATG12 and ATG16L2) in 393 North American NSCLC patients treated by definitive radiotherapy and assessed their associations with RP, local recurrence-free survival (LRFS), progression-free survival (PFS) and overall survival (OS) in multivariable Cox proportional hazards regression analyses.We found that the ATG16L2 rs10898880 CC variant genotype had a better LRFS, PFS and OS [adjusted hazards ratio (adjHR) = 0.59, 0.64 and 0.64; 95% confidence interval (95% CI = 0.45-0.79, 0.48-0.84 and 0.48-0.86); and P = 0.0004, 0.002 and 0.003, respectively], but a greater risk of developing severe RP (adjHR = 1.80, 96% CI = 1.04-3.12, P = 0.037), than patients with CC/CT genotypes. Further functional analyses suggested that the ATG16L2 rs10898880 C variant allele modulated the expression of the ATG16L2 gene.This is the first report that functional ATG16L2 C variant homozygous genotype may be a predictor of RP, LRFS, PFS, and OS in NSCLC patients after definitive radiotherapy. Additional larger, prospective studies are needed to confirm these findings.

Authors

Wen, J; Liu, H; Wang, L; Wang, X; Gu, N; Liu, Z; Xu, T; Gomez, DR; Komaki, R; Liao, Z; Wei, Q

MLA Citation

Wen, J, Liu, H, Wang, L, Wang, X, Gu, N, Liu, Z, Xu, T, Gomez, DR, Komaki, R, Liao, Z, and Wei, Q. "Potentially Functional variants of ATG16L2 predict radiation pneumonitis and outcomes in patients with non-small cell lung cancer after definitive radiotherapy." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (February 15, 2018).

PMID

29454863

Source

epmc

Published In

Journal of Thoracic Oncology

Publish Date

2018

DOI

10.1016/j.jtho.2018.01.028

Nucleotide excision repair (NER) plays a vital role in platinum-induced DNA damage during chemotherapy. We hypothesize that regulatory single nucleotide polymorphisms (rSNPs) of the core NER genes modulate clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy (PBS). We investigated associations of 25 rSNPs in eight NER genes with progression free survival (PFS) and overall survival (OS) in 710 NSCLC patients. We found that ERCC1 rs3212924 AG/GG and XPC rs2229090 GC/CC genotypes were associated with patients' PFS (HRadj = 1.21, 95% CI = 1.03-1.43, P adj = 0.021 for ERCC1 and HRadj = 0.80, 95% CI = 0.68-0.94, P adj = 0.007 for XPC), compared with the AA and GG genotypes, respectively. The association of XPC rs2229090 was more apparent in adenocarcinoma than in squamous cell carcinoma patients. Additionally, ERCC4 rs1799798 GA/AA genotypes were associated with poorer OS (HRadj = 1.32, 95% CI = 1.04-1.69, P adj = 0.026), compared with the GG genotype. The expression quantitative trait loci analysis revealed that ERCC1 rs3212924 and XPC rs2229090 might regulate transcription of their genes, which is consistent with their associations with survival. Larger studies are needed to validate our findings with further functional studies to elucidate the mechanisms underlying these observed associations.

Authors

Zhang, R; Jia, M; Xue, H; Xu, Y; Wang, M; Zhu, M; Sun, M; Chang, J; Wei, Q

MLA Citation

Zhang, R, Jia, M, Xue, H, Xu, Y, Wang, M, Zhu, M, Sun, M, Chang, J, and Wei, Q. "Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung cancer patients treated with platinum-based therapy." Scientific reports 7.1 (September 6, 2017): 10702-.

PMID

28878296

Source

epmc

Published In

Scientific Reports

Volume

7

Issue

1

Publish Date

2017

Start Page

10702

DOI

10.1038/s41598-017-10800-5

Cutaneous melanoma (CM) is the most lethal skin cancer. The Wnt pathway has an impact on development, invasion, and metastasis of CM, thus likely affecting CM prognosis. Using data from a published genome-wide association study from The University of Texas MD Anderson Cancer Center, we assessed the associations of 19,830 common single-nucleotide polymorphisms (SNPs) in 151 Wnt pathway autosomal genes with CM-specific survival and then validated significant SNPs in another genome-wide association study from Harvard University. In the single-locus analysis, 1,855 SNPs were significantly associated with CM-specific survival at P < 0.05, of which 547 SNPs were still considered noteworthy after the correction by the false-positive report probability. In the replication, two SNPs remained significantly associated with CM-specific survival after multiple comparison correction. By performing functional prediction and stepwise selection, we identified two independent SNPs (i.e., WNT2B rs1175649 G>T and BTRC rs61873997 G>A) that showed a predictive role in CM-specific survival, with an effect-allele-attributed hazards ratio (adjusted hazards ratio) of 1.99 (95% confidence interval = 1.41-2.81, P = 8.10 × 10-5) and 0.61 (0.46-0.80, 3.12×10-4), respectively. Collectively, these variants in the Wnt pathway genes may be biomarkers for outcomes of patients with CM, if validated by larger studies.

Authors

Shi, Q; Liu, H; Han, P; Li, C; Wang, Y; Wu, W; Zhu, D; Amos, CI; Fang, S; Lee, JE; Han, J; Wei, Q

MLA Citation

Shi, Q, Liu, H, Han, P, Li, C, Wang, Y, Wu, W, Zhu, D, Amos, CI, Fang, S, Lee, JE, Han, J, and Wei, Q. "Genetic Variants in WNT2B and BTRC Predict Melanoma Survival." The Journal of investigative dermatology 137.8 (August 2017): 1749-1756.

PMID

28499756

Source

epmc

Published In

Journal of Investigative Dermatology

Volume

137

Issue

8

Publish Date

2017

Start Page

1749

End Page

1756

DOI

10.1016/j.jid.2017.04.023

The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling events mediated by TCPTP. Mutations and genetic variants of some genes in the TCPTP pathway are associated with lung cancer risk and survival. In the present study, we first investigated associations of 5,162 single nucleotide polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by using summary data of six published genome-wide association studies (GWAS) of 12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight genes after correction for multiple comparisons by a false discovery rate <0.20. Then, we performed in silico functional analyses for these 11 SNPs by eQTL analysis, two of which, PTPN2 SNPs rs2847297 and rs2847282, were chosen as tagSNPs. We further included two additional GWAS datasets of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls), and the overall effects of these two SNPs among all eight GWAS studies remained significant (OR = 0.95, 95% CI = 0.92-0.98, and P = 0.004 for rs2847297; OR = 0.95, 95% CI = 0.92-0.99, and P = 0.009 for rs2847282). In conclusion, the PTPN2 rs2847297 and rs2847282 may be potential susceptible loci for lung cancer risk.

Authors

Feng, Y; Wang, Y; Liu, H; Liu, Z; Mills, C; Han, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeboeller, H; Rosenberger, A; Houlston, RS; Caporaso, NE; Teresa Landi, M; Brueske, I; Risch, A; Ye, Y; Wu, X; Christiani, DC; Amos, CI; Wei, Q

MLA Citation

Feng, Y, Wang, Y, Liu, H, Liu, Z, Mills, C, Han, Y, Hung, RJ, Brhane, Y, McLaughlin, J, Brennan, P, Bickeboeller, H, Rosenberger, A, Houlston, RS, Caporaso, NE, Teresa Landi, M, Brueske, I, Risch, A, Ye, Y, Wu, X, Christiani, DC, Amos, CI, and Wei, Q. "Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium." Scientific reports 7.1 (April 11, 2017): 825-.

PMID

28400551

Source

epmc

Published In

Scientific Reports

Volume

7

Issue

1

Publish Date

2017

Start Page

825

DOI

10.1038/s41598-017-00850-0

Tobacco smoke and alcohol drinking are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN). Smoking and drinking cause DNA damage leading to apoptosis, and insufficient apoptotic capacity may favour development of cancer because of the dysfunction of removing damaged cells. In the present study, we investigated the association between camptothecin (CPT)-induced apoptotic capacity and risk of SCCHN in a North American population.In a case-control study of 708 SCCHN patients and 685 matched cancer-free controls, we measured apoptotic capacity in cultured peripheral blood lymphocytes in response to in vitro exposure to CPT by using the flow cytometry-based method.We found that the mean level of apoptotic capacity in the cases (45.9 ± 23.3%) was significantly lower than that in the controls (49.0 ± 23.1%) (P = 0.002). When we used the median level of apoptotic capacity in the controls as the cutoff value for calculating adjusted odds ratios, subjects with a reduced apoptotic capacity had an increased risk (adjusted odds ratio = 1.42, 95% confidence interval = 1.13-1.78, P = 0.002), especially for those who were age ≥57 (1.73, 1.25-2.38, 0.0009), men (1.76, 1.36-2.27, <0.0001) and ever drinkers (1.67, 1.27-2.21, 0.0003), and these variables significantly interacted with apoptotic capacity (Pinteraction = 0.015, 0.005 and 0.009, respectively). A further fitted prediction model suggested that the inclusion of apoptotic capacity significantly improved in the prediction of SCCHN risk.Individuals with a reduced CPT-induced apoptotic capacity may be at an increased risk of developing SCCHN, and apoptotic capacity may be a biomarker for susceptibility to SCCHN.

Authors

Liu, Z; Liu, H; Han, P; Gao, F; Dahlstrom, KR; Li, G; Owzar, K; Zevallos, JP; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Liu, H, Han, P, Gao, F, Dahlstrom, KR, Li, G, Owzar, K, Zevallos, JP, Sturgis, EM, and Wei, Q. "Apoptotic capacity and risk of squamous cell carcinoma of the head and neck." European journal of cancer (Oxford, England : 1990) 72 (February 2017): 166-176.

PMID

28033527

Source

epmc

Published In

European Journal of Cancer

Volume

72

Publish Date

2017

Start Page

166

End Page

176

DOI

10.1016/j.ejca.2016.11.018

The Piwi-piRNA pathway is important for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control and thus may be involved in cancer development. In this study, we comprehensively analyzed prognostic roles of 3,116 common SNPs in PIWI-piRNA pathway genes in melanoma disease-specific survival. A published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used to identify associated SNPs, which were later validated by another GWAS from the Harvard Nurses' Health Study and Health Professionals Follow-up Study. After multiple testing correction, we found that there were 27 common SNPs in two genes (PIWIL4 and DCP1A) with false discovery rate < 0.2 in the discovery dataset. Three tagSNPs (i.e., rs7933369 and rs508485 in PIWIL4; rs11551405 in DCP1A) were replicated. The rs11551405 A allele, located at the 3' UTR microRNA binding site of DCP1A, was associated with an increased risk of melanoma disease-specific death in both discovery dataset [adjusted Hazards ratio (HR) = 1.66, 95% confidence interval (CI) = 1.21-2.27, p =1.50 × 10-3 ] and validation dataset (HR = 1.55, 95% CI = 1.03-2.34, p = 0.038), compared with the C allele, and their meta-analysis showed an HR of 1.62 (95% CI, 1.26-2.08, p =1.55 × 10-4 ). Using RNA-seq data from the 1000 Genomes Project, we found that DCP1A mRNA expression levels increased significantly with the A allele number of rs11551405. Additional large, prospective studies are needed to validate these findings.

Authors

Zhang, W; Liu, H; Yin, J; Wu, W; Zhu, D; Amos, CI; Fang, S; Lee, JE; Li, Y; Han, J; Wei, Q

MLA Citation

Zhang, W, Liu, H, Yin, J, Wu, W, Zhu, D, Amos, CI, Fang, S, Lee, JE, Li, Y, Han, J, and Wei, Q. "Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival." International journal of cancer 139.12 (December 2016): 2730-2737.

PMID

27578485

Source

epmc

Published In

International Journal of Cancer

Volume

139

Issue

12

Publish Date

2016

Start Page

2730

End Page

2737

DOI

10.1002/ijc.30409

The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR]=1.39; 95% confidence interval [CI]=1.16-1.66; P=.0003) and OS (adjusted HR=1.41; 95% CI=1.11-1.80; P=.005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR=0.86; 95% CI=0.56-1.33; P=.505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.

Authors

Jia, M; Xu, Y; Zhu, M; Wang, M; Sun, M; Qian, J; Chang, J; Wei, Q

MLA Citation

Jia, M, Xu, Y, Zhu, M, Wang, M, Sun, M, Qian, J, Chang, J, and Wei, Q. "The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non-Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy." Translational oncology 9.6 (December 2016): 531-539.

PMID

27835790

Source

epmc

Published In

Translational oncology

Volume

9

Issue

6

Publish Date

2016

Start Page

531

End Page

539

DOI

10.1016/j.tranon.2016.09.006

Breslow thickness (BT) is a major prognostic factor of cutaneous melanoma (CM), the most fatal skin cancer. The genetic component of BT has only been explored by candidate gene studies with inconsistent results. Our objective was to uncover the genetic factors underlying BT using an hypothesis-free genome-wide approach. Our analysis strategy integrated a genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) for BT followed by pathway analysis of GWAS outcomes using the gene-set enrichment analysis (GSEA) method and epistasis analysis within BT-associated pathways. This strategy was applied to two large CM datasets with Hapmap3-imputed SNP data: the French MELARISK study for discovery (966 cases) and the MD Anderson Cancer Center study (1,546 cases) for replication. While no marginal effect of individual SNPs was revealed through GWAS, three pathways, defined by gene ontology (GO) categories were significantly enriched in genes associated with BT (false discovery rate ≤5% in both studies): hormone activity, cytokine activity and myeloid cell differentiation. Epistasis analysis, within each significant GO, identified a statistically significant interaction between CDC42 and SCIN SNPs (pmeta-int =2.2 × 10(-6) , which met the overall multiple-testing corrected threshold of 2.5 × 10(-6) ). These two SNPs (and proxies) are strongly associated with CDC42 and SCIN gene expression levels and map to regulatory elements in skin cells. This interaction has important biological relevance since CDC42 and SCIN proteins have opposite effects in actin cytoskeleton organization and dynamics, a key mechanism underlying melanoma cell migration and invasion.

Authors

Vaysse, A; Fang, S; Brossard, M; Wei, Q; Chen, WV; Mohamdi, H; Vincent-Fetita, L; Margaritte-Jeannin, P; Lavielle, N; Maubec, E; Lathrop, M; Avril, M-F; Amos, CI; Lee, JE; Demenais, F

MLA Citation

Vaysse, A, Fang, S, Brossard, M, Wei, Q, Chen, WV, Mohamdi, H, Vincent-Fetita, L, Margaritte-Jeannin, P, Lavielle, N, Maubec, E, Lathrop, M, Avril, M-F, Amos, CI, Lee, JE, and Demenais, F. "A comprehensive genome-wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants." International journal of cancer 139.9 (November 2016): 2012-2020.

PMID

27347659

Source

epmc

Published In

International Journal of Cancer

Volume

139

Issue

9

Publish Date

2016

Start Page

2012

End Page

2020

DOI

10.1002/ijc.30245

DNA repair pathways maintain genomic integrity and stability, and dysfunction of DNA repair leads to cancer. We hypothesize that functional genetic variants in DNA repair genes are associated with risk of lung cancer. We performed a large-scale meta-analysis of 123,371 single nucleotide polymorphisms (SNPs) in 169 DNA repair genes obtained from six previously published genome-wide association studies (GWASs) of 12160 lung cancer cases and 16838 controls. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) using the logistic regression model and used the false discovery rate (FDR) method for correction of multiple testing. As a result, 14 SNPs had a significant odds ratio (OR) for lung cancer risk with P FDR < 0.05, of which rs3115672 in MSH5 (OR = 1.20, 95% CI = 1.14-1.27) and rs114596632 in GTF2H4 (OR = 1.19, 95% CI = 1.12-1.25) at 6q21.33 were the most statistically significant (P combined = 3.99×10(-11) and P combined = 5.40×10(-10), respectively). The MSH5 rs3115672, but not GTF2H4 rs114596632, was strongly correlated with MSH5 rs3131379 in that region (r (2) = 1.000 and r (2) = 0.539, respectively) as reported in a previous GWAS. Importantly, however, the GTF2H4 rs114596632 T, but not MSH5 rs3115672 T, allele was significantly associated with both decreased DNA repair capacity phenotype and decreased mRNA expression levels. These provided evidence that functional genetic variants of GTF2H4 confer susceptibility to lung cancer.

Authors

Wang, M; Liu, H; Liu, Z; Yi, X; Bickeboller, H; Hung, RJ; Brennan, P; Landi, MT; Caporaso, N; Christiani, DC; Doherty, JA; TRICL Research Team, ; Amos, CI; Wei, Q

MLA Citation

Wang, M, Liu, H, Liu, Z, Yi, X, Bickeboller, H, Hung, RJ, Brennan, P, Landi, MT, Caporaso, N, Christiani, DC, Doherty, JA, TRICL Research Team, , Amos, CI, and Wei, Q. "Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium." Carcinogenesis 37.9 (September 2016): 888-896.

PMID

27288692

Source

epmc

Published In

Carcinogenesis

Volume

37

Issue

9

Publish Date

2016

Start Page

888

End Page

896

DOI

10.1093/carcin/bgw070

The immune system has important roles in tumor development and outcomes after cancer treatment. We evaluated whether single-nucleotide polymorphisms (SNPs) in the gene encoding casitas B-lineage lymphoma b protein (Cbl-b), an E3 ubiquitin ligase that maintains immune tolerance by negatively regulating T-cell activation and function, were associated with outcomes after treatment of non-small-cell lung cancer (NSCLC).Samples from 393 patients with NSCLC treated with definitive radiotherapy at a single institution between March 1998 and February 2009 were used to genotype 3 potentially functional SNPs in CBLB (rs1042852 C>T, rs2305035 G>A, and rs7649466 C>G). We evaluated associations between these SNPs and local recurrence-free survival, distant metastasis-free survival, overall survival, and risk of radiation pneumonitis (RP).Having the rs2305035 A variant genotypes (AA or AG) was associated with better local recurrence-free survival (median 15.8 vs. 15.3 months; adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.60-0.98; P = .033), distant metastasis-free survival (median 15.4 vs. 14.0 months; adjusted HR, 0.74; 95% CI, 0.57-0.96; P = .024) and overall survival (median 23.5 vs. 22.8 months; adjusted HR, 0.72; 95% CI, 0.56-0.93; P = .013) after adjustment in a Cox proportional hazard model. Patients with these genotypes were also at greater risk of developing grade 3 or higher RP than were patients with GG genotypes in an adjusted Cox proportional hazard model.This is the first report that rs2305035 genotypes in CBLB were associated with clinical and RP risk among patients with NSCLC treated with definitive radiotherapy. These findings could assist in generating hypothesis for further mechanistic studies.

Authors

Li, P; Wang, X; Liu, Z; Liu, H; Xu, T; Wang, H; Gomez, DR; Nguyen, Q-N; Wang, L-E; Teng, Y; Song, Y; Komaki, R; Welsh, JW; Wei, Q; Liao, Z

MLA Citation

Li, P, Wang, X, Liu, Z, Liu, H, Xu, T, Wang, H, Gomez, DR, Nguyen, Q-N, Wang, L-E, Teng, Y, Song, Y, Komaki, R, Welsh, JW, Wei, Q, and Liao, Z. "Single Nucleotide Polymorphisms in CBLB, a Regulator of T-Cell Response, Predict Radiation Pneumonitis and Outcomes After Definitive Radiotherapy for Non-Small-Cell Lung Cancer." Clinical lung cancer 17.4 (July 2016): 253-262.e5.

PMID

26732495

Source

epmc

Published In

Clinical lung cancer

Volume

17

Issue

4

Publish Date

2016

Start Page

253

End Page

262.e5

DOI

10.1016/j.cllc.2015.11.008

Several studies have reported that cigarette smoking is inversely associated with the risk of melanoma. This study further tested whether incorporating genetic factors will provide another level of evaluation of mechanisms underlying the association between smoking and risk of melanoma. We investigated the association between SNPs selected from genome-wide association studies (GWAS) on smoking behaviors and risk of melanoma using 2,298 melanoma cases and 6,654 controls. Among 16 SNPs, three (rs16969968 [A], rs1051730 [A] and rs2036534 [C] in the 15q25.1 region) reached significance for association with melanoma risk in men (0.01 < = P values < = 0.02; 0.85 < = Odds Ratios (ORs) <= 1.20). There was association between the genetic scores based on the number of smoking behavior-risk alleles and melanoma risk with P-trend = 0.005 among HPFS. Further association with smoking behaviors indicating those three SNPs (rs16969968 [A], rs1051730 [A] and rs2036534 [C]) significantly associated with number of cigarettes smoked per day, CPD, with P = 0.009, 0.011 and 0.001 respectively. The SNPs rs215605 in the PDE1C gene and rs6265 in the BDNF gene significantly interacted with smoking status on melanoma risk (interaction P = 0.005 and P = 0.003 respectively). Our study suggests that smoking behavior-related SNPs are likely to play a role in melanoma development and the potential public health importance of polymorphisms in the CHRNA5-A3-B4 gene cluster. Further larger studies are warranted to validate the findings.

Authors

Wu, W; Liu, H; Song, F; Chen, L-S; Kraft, P; Wei, Q; Han, J

MLA Citation

Wu, W, Liu, H, Song, F, Chen, L-S, Kraft, P, Wei, Q, and Han, J. "Associations between smoking behavior-related alleles and the risk of melanoma." Oncotarget 7.30 (July 2016): 47366-47375.

Website

http://hdl.handle.net/10161/12519

PMID

27344179

Source

epmc

Published In

Oncotarget

Volume

7

Issue

30

Publish Date

2016

Start Page

47366

End Page

47375

DOI

10.18632/oncotarget.10144

DNA double-strand breaks (DSBs) are one of the most serious forms of DNA damage to the cell, causing genomic instability and ultimately carcinogenesis. In this study, we hypothesized that single nucleotide polymorphisms (SNPs) at the micro RNA (miRNA)-binding sites of DSB repair genes may influence cancer risk by dysregulating target gene expression. To test our hypothesis, we firstly performed functional prediction for common SNPs in DSB genes and found 12 potentially functional SNPs located at the miRNA-binding sites. We then investigated their associations with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1087 patients and 1090 cancer-free controls in a non-Hispanic white population. As a result, SNP rs7213430 in BRIP1 was found to be significantly associated with cancer risk (P trend = 0.021). Compared with the AA homozygotes, the G allele carriers had an increased risk of SCCHN (adjusted OR 1.16, 95 % CI 1.02-1.31). Marginal significance was found for another SNP rs15869 in BRCA2 (P = 0.053). Further, functional analyses showed that SNP rs7213430 is within the miR-101 seed-binding region, and the variant G allele could lead to significantly lower luciferase activity and BRIP1 mRNA expression, compared to the A allele with the presence of miR-101. Our results suggested that SNP rs7213430 in the 3'-UTR of BRIP1 might contribute to SCCHN susceptibility by affecting the binding activity of miR-101 and resulting in a decreased BRIP1 expression. Additional larger population and functional studies are warranted to confirm our findings.

Authors

Liu, H; Gao, F; Dahlstrom, KR; Li, G; Sturgis, EM; Zevallos, JP; Wei, Q; Liu, Z

MLA Citation

Liu, H, Gao, F, Dahlstrom, KR, Li, G, Sturgis, EM, Zevallos, JP, Wei, Q, and Liu, Z. "A variant at a potentially functional microRNA-binding site in BRIP1 was associated with risk of squamous cell carcinoma of the head and neck." Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37.6 (June 2016): 8057-8066.

PMID

26711789

Source

epmc

Published In

Tumor Biology

Volume

37

Issue

6

Publish Date

2016

Start Page

8057

End Page

8066

DOI

10.1007/s13277-015-4682-6

Cell membrane transporters and metabolic enzymes play a crucial role in the transportation of a wide variety of substrates that maintain homeostasis in biological processes. We explored associations between genetic variants in these genes and survival of nonsmall-cell lung cancer (NSCLC) patients by reanalyzing two datasets from published genome-wide association studies (GWASs). In the discovery by using the GWAS dataset of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, we evaluated associations of 1,245 single-nucleotide polymorphisms (SNPs) in genes of four transporter families and two metabolic enzyme families with survival of 1,185 NSCLC patients. We then performed a replication analysis in the Harvard University Lung Cancer study (LCS) with 984 NSCLC patients. Multivariate Cox proportional hazards regression and false discovery rate (FDR) corrections were performed to evaluate the associations. We identified that 21 genotyped SNPs in eight gene regions were significantly associated with survival with FDR ≤ 0.1 in the discovery dataset. Subsequently, we confirmed six SNPs, which were putative functional, in ABCG1 of the ATP-binding cassette transporter family in the replication dataset. In the pooled analysis, two tagging (at r(2)  > 0.8 for linkage disequilibrium with other replicated SNPs)/functional SNPs were independently associated with survival: rs225388 G > A [adjusted hazards ratio (HR) = 1.12, 95% confidence interval (CI) = 1.03-1.20, Ptrend  = 4.6 × 10(-3)] and rs225390 A > G (adjusted HR = 1.16, 95% CI = 1.07-1.25, Ptrend  = 3.8 × 10(-4) ). Our results indicated that genetic variants of ABCG1 may be predictors of survival of NSCLC patients.

Authors

Wang, Y; Liu, H; Ready, NE; Su, L; Wei, Y; Christiani, DC; Wei, Q

MLA Citation

Wang, Y, Liu, H, Ready, NE, Su, L, Wei, Y, Christiani, DC, and Wei, Q. "Genetic variants in ABCG1 are associated with survival of nonsmall-cell lung cancer patients." International journal of cancer 138.11 (June 2016): 2592-2601.

PMID

26757251

Source

epmc

Published In

International Journal of Cancer

Volume

138

Issue

11

Publish Date

2016

Start Page

2592

End Page

2601

DOI

10.1002/ijc.29991

IL-1a, an important regulator of immune and inflammation responses, has been implicated in cancer development and prognosis. An insertion (Ins)/deletion (Del) polymorphism (IL-1a rs3783553) in the 3' UTR of IL-1a may disrupt a binding site for miRNA-122 and may affect its transcription level. Thus, this polymorphism may cause interindividual variation in immune and inflammation responses and thus may lead to different susceptibility to treatment response and prognosis of such patients. We evaluated the association of IL-1a rs3783553 polymorphism with risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate associations. Compared with patients with Del/Del homozygous genotype, the patients with Ins/Del+Ins/Ins variant genotypes had worse disease-free survival (log-rank P < 0.0001) and increased risk of SCCOP recurrence (HR, 2.4, 95% CI, 1.7-3.3) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with Ins/Del+Ins/Ins variant genotypes of the IL-1a polymorphism had worse disease-free survival (log-rank P < 0.0001) and much higher recurrence risk than those with Del/Del homozygous genotype of this polymorphism (HR, 16.3, 95% CI, 5.0-52.7). Our findings suggest that IL-1a rs3783553 polymorphism may modulate the risk of SCCOP recurrence in patients, particularly for patients with HPV16-positive tumors. However, larger studies are needed to validate these results.

Authors

Wang, C; Sturgis, EM; Chen, X; Wei, Q; Li, G

MLA Citation

Wang, C, Sturgis, EM, Chen, X, Wei, Q, and Li, G. "A functional variant at miRNA-122 binding site in IL-1a 3' UTR predicts risk of recurrence in patients with oropharyngeal cancer." Oncotarget 7.23 (June 2016): 34472-34479.

PMID

27121322

Source

epmc

Published In

Oncotarget

Volume

7

Issue

23

Publish Date

2016

Start Page

34472

End Page

34479

DOI

10.18632/oncotarget.8908

Common single nucleotide polymorphisms (SNPs) in miRNAs may affect miRNA functions and their target expression and thus may affect biological activities and cancer etiology as well as prognosis. Thus, we determined whether the 9 SNPs in microRNAs modify the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. We found that the SNPs in the miRNA146, miRNA196, and Gemin3 were associated with a significantly reduced and increased risk of SCCOP recurrence after multivariate adjustment (aHR, 0.6, 95%CI, 0.4-0.9, aHR, 2.1, 95%CI, 1.6-2.8, and aHR, 0.6, 95%CI, 0.5-0.9, respectively). Furthermore, the similar effect of these 3 SNPs on SCCOP recurrence risk was found in HPV-positive SCCOP patients only. However, no significant associations were found for other SNPs. To evaluate the aggregate effects of these SNPs, we performed a combined risk genotype analysis. We found that, compared with the low-risk reference group with less than 4 risk genotypes, the medium-risk group with 4 or 5 risk genotypes exhibited a 1.7-fold (1.2-2.4) increased risk whereas the high-risk group with more than 5 risk genotypes exhibited a 3.0-fold (1.7-4.2) increased risk (Ptrend < 0.001). Such combined effects were particularly pronounced in HPV-positive SCCOP patients. Taken together, this is the first study with a large cohort of SCCOP patients showing that miRNA-related genetic variants may modify risk of SCCOP recurrence individually and jointly. Larger studies are needed to validate these results.

Authors

Chen, X; Sturgis, EM; Wang, C; Cao, X; Li, Y; Wei, Q; Li, G

MLA Citation

Chen, X, Sturgis, EM, Wang, C, Cao, X, Li, Y, Wei, Q, and Li, G. "Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy." Oncotarget 7.23 (June 2016): 35015-35025.

PMID

27145460

Source

epmc

Published In

Oncotarget

Volume

7

Issue

23

Publish Date

2016

Start Page

35015

End Page

35025

DOI

10.18632/oncotarget.9014

Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.

Authors

Zhou, F; Zhu, M; Wang, M; Qiu, L; Cheng, L; Jia, M; Xiang, J; Wei, Q

MLA Citation

Zhou, F, Zhu, M, Wang, M, Qiu, L, Cheng, L, Jia, M, Xiang, J, and Wei, Q. "Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy." Journal of translational medicine 14.1 (May 31, 2016): 154-.

PMID

27246611

Source

epmc

Published In

Journal of Translational Medicine

Volume

14

Issue

1

Publish Date

2016

Start Page

154

DOI

10.1186/s12967-016-0903-z

To evaluate for an association between 25-hydroxyvitamin D levels (vitamin D) and outcome measures in patients with melanoma after evaluation is controlled for systemic inflammatory response (SIR) on the basis of simultaneous C-reactive protein (CRP) measurement.Plasma samples from 1,042 prospectively observed patients with melanoma were assayed for vitamin D and CRP. The associations of demographics and CRP with vitamin D were determined, followed by a determination of the association between vitamin D and stage and outcome measures from the date of blood draw. The vitamin D level was considered sufficient if it was 30 to 100 ng/mL. Kaplan-Meier and Cox regression analyses were performed.The median vitamin D level was 25.0 ng/mL. The median follow-up time was 7.1 years. A lower vitamin D was associated with the blood draw during fall/winter months (P < .001), older age (P = .001), increased CRP (P < .001), increased tumor thickness (P < .001), ulcerated tumor (P = .0105), and advanced melanoma stage (P = .0024). On univariate analysis, lower vitamin D was associated with poorer overall (OS; P < .001), melanoma-specific survival (MSS; P = .0025), and disease-free survival (DFS; P = .0466). The effect of vitamin D on these outcome measures persisted after adjustment for CRP and other covariates. Multivariable hazards ratios per unit decrease of vitamin D were 1.02 for OS (95% CI, 1.01 to 1.04; P = .0051), 1.02 for MSS (95% CI, 1.00 to 1.04; P = .048), and 1.02 for DFS (95% CI, 1.00 to 1.04; P = .0427).Lower vitamin D levels in patients with melanoma were associated with poorer outcomes. Although lower vitamin D was strongly associated with higher CRP, the associations of lower vitamin D with poorer OS, MSS, and DFS were independent of this association. Investigation of mechanisms responsible for these associations may be of value to patients with melanoma.

Authors

Fang, S; Sui, D; Wang, Y; Liu, H; Chiang, Y-J; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Wargo, J; Hu, MI; Gardner, JM; Reveille, JD; Bassett, RL; Wei, Q; Amos, CI; Lee, JE

MLA Citation

Fang, S, Sui, D, Wang, Y, Liu, H, Chiang, Y-J, Ross, MI, Gershenwald, JE, Cormier, JN, Royal, RE, Lucci, A, Wargo, J, Hu, MI, Gardner, JM, Reveille, JD, Bassett, RL, Wei, Q, Amos, CI, and Lee, JE. "Association of Vitamin D Levels With Outcome in Patients With Melanoma After Adjustment For C-Reactive Protein." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.15 (May 2016): 1741-1747.

PMID

27001565

Source

epmc

Published In

Journal of Clinical Oncology

Volume

34

Issue

15

Publish Date

2016

Start Page

1741

End Page

1747

DOI

10.1200/jco.2015.64.1357

The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.

Authors

Jia, M; Zhu, M; Wang, M; Sun, M; Qian, J; Ding, F; Chang, J; Wei, Q

MLA Citation

Jia, M, Zhu, M, Wang, M, Sun, M, Qian, J, Ding, F, Chang, J, and Wei, Q. "Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer." Oncotarget 7.18 (May 2016): 25291-25303.

PMID

26993769

Source

epmc

Published In

Oncotarget

Volume

7

Issue

18

Publish Date

2016

Start Page

25291

End Page

25303

DOI

10.18632/oncotarget.8052

The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.

Authors

Zhou, F; Cheng, L; Qiu, L-X; Wang, M-Y; Li, J; Sun, M-H; Yang, Y-J; Wang, J-C; Jin, L; Wang, Y-N; Wei, Q-Y

MLA Citation

Zhou, F, Cheng, L, Qiu, L-X, Wang, M-Y, Li, J, Sun, M-H, Yang, Y-J, Wang, J-C, Jin, L, Wang, Y-N, and Wei, Q-Y. "Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population." Oncotarget 7.19 (May 2016): 28112-28123.

PMID

27049718

Source

epmc

Published In

Oncotarget

Volume

7

Issue

19

Publish Date

2016

Start Page

28112

End Page

28123

DOI

10.18632/oncotarget.8492

Functional polymorphisms of miRNAs may affect the function and target expression of miRNAs, which can, in turn, affect the biological activity, etiology, and prognosis of cancer. We hypothesized that four common polymorphisms in pre-miRNAs (hsa-mir-146a rs2910164 G > C, hsa-mir-196a2 rs11614913 C > T, hsa-mir-149 rs2292832 G > T, and hsa-mir-499 rs3746444 A > G) are associated with survival in SCCNOP. We used univariate and multivariable Cox models to evaluate the associations between the four polymorphisms and survival. We found that hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 had statistically significant associations with survival, but hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913 did not. Patients having the hsa-mir-149 CC and hsa-mir-499 TT wild-type genotypes had significantly better overall, disease-specific, and disease-free survival compared with those who had the corresponding variant CT/TT and CT/CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders, indicating that these pre-miRNA polymorphisms may be prognostic biomarkers for SCCNOP. Moreover, the stratified analyses based on smoking status and treatment indicated that the effects of hsa-mir-149 and hsa-mir-499 polymorphisms on survival were more pronounced in ever smokers and patients treated with chemoradiation. Our findings support that the hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 polymorphisms play a significant role in the prognosis of SCCNOP, especially in smokers and patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings.

Authors

Wang, C; Sturgis, EM; Chen, X; Zheng, H; Wei, Q; Li, G

MLA Citation

Wang, C, Sturgis, EM, Chen, X, Zheng, H, Wei, Q, and Li, G. "Pre-miRNA variants as predictors of clinical outcome in patients with squamous cell carcinomas of the nonoropharynx." Oncotarget 7.18 (May 2016): 26444-26453.

PMID

27050146

Source

epmc

Published In

Oncotarget

Volume

7

Issue

18

Publish Date

2016

Start Page

26444

End Page

26453

DOI

10.18632/oncotarget.8512

Human papillomavirus (HPV) is a causal and prognostic factor for oropharyngeal cancer, but its role in squamous cell carcinoma of the oral cavity (SCCOC) is unclear. We sought to clarify HPV's role in SCCOC.Patients with newly diagnosed SCCOC (N=460) were prospectively recruited, treated, and followed at one institution. p16/HPV status was determined by p16 immunohistochemistry (IHC) (N=210), PCR-based HPV 16/18 E6/7 DNA testing (N=403), and/or HPV in situ hybridization (ISH) (N=178). Kaplan-Meier curves and log-rank tests were used to compare survival by p16/HPV status.p16 expression was detected in 30% of tumors (62/210) and HPV 16/18 E6/7 DNA in 28% (114/403), although correlation between these two assays was poor (r=-0.01). Patients with p16-positive tumors were more likely to be younger and have primary tumors of the oral tongue. Only 4% of tumors (7/171) were positive for HPV by ISH. Comparisons of patients with p16-positive and p16-negative tumors, patients with HPV-positive and HPV-negative tumors by PCR, and patients with HPV-positive and HPV-negative tumors by ISH showed no significant differences in disease-specific or disease-free survival by p16/HPV status. When we applied a more stringent definition of HPV positivity based on a combination of assay results, only 10 of 166 tumors were HPV positive, and there were no significant differences in demographic, exposure, clinical, or survival characteristics between these patients and the 156 HPV-negative patients.Very few patients with SCCOC have HPV-driven tumors. SCCOC that overexpresses p16 may be a unique subset deserving of further study.

Authors

Zafereo, ME; Xu, L; Dahlstrom, KR; Viamonte, CA; El-Naggar, AK; Wei, Q; Li, G; Sturgis, EM

MLA Citation

Zafereo, ME, Xu, L, Dahlstrom, KR, Viamonte, CA, El-Naggar, AK, Wei, Q, Li, G, and Sturgis, EM. "Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus." Oral oncology 56 (May 2016): 47-53.

PMID

27086486

Source

epmc

Published In

Oral Oncology

Volume

56

Publish Date

2016

Start Page

47

End Page

53

DOI

10.1016/j.oraloncology.2016.03.003

Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case-control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 μmol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P=0.004) and was associated with an increased risk for CM (adjusted odds ratio=1.78, 95% confidence interval: 1.12-2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (P(trend)=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (P(interaction)=0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromotid breaks.

Authors

Wang, L-E; Li, C; Xiong, P; Gershenwald, JE; Prieto, VG; Duvic, M; Lee, JE; Grimm, EA; Hsu, TC; Wei, Q

MLA Citation

Wang, L-E, Li, C, Xiong, P, Gershenwald, JE, Prieto, VG, Duvic, M, Lee, JE, Grimm, EA, Hsu, TC, and Wei, Q. "4-nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis." Melanoma research 26.2 (April 2016): 181-187.

PMID

24977319

Source

epmc

Published In

Melanoma Research

Volume

26

Issue

2

Publish Date

2016

Start Page

181

End Page

187

DOI

10.1097/cmr.0000000000000106

Esophageal squamous cell carcinoma (ESCC) is the dominant type of esophageal cancer in the East Asian population. MicroRNAs (miRNAs) have been studied to play important roles in tumorigenesis. Single nucleotide polymorphisms (SNPs) in miRNA lead to the aberrant expression and structural alteration of miRNA and are hypothesized to be involved in tumorigenesis and cancer development. We conducted a population-based case-control study to evaluate the association between SNPs in miRNAs and ESCC risk in 1400 ESCC cases and 2185 matched controls. Four SNPs including miR-196a2 rs11614913, miR-146a rs2910164, miR-499 rs3746444, and miR-423 rs6505162 were selected with comprehensive collection strategy and genotyped using the SNaPshot Multiplex System. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of association. The CC genotype of miR-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype (OR 1.11, 95 % CI 1.01-1.22, P 0.049) and the TT/TC genotypes (OR 1.09, 95 % CI 1.01-1.19, P 0.043). The association was more pronounced in non-drinkers in the recessive model (OR 1.13, 95 % CI 1.01-1.27, P 0.029). A significantly increased risk of ESCC associated with miR-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. This study suggests that miR-196a2 rs11614913 and miR-499 rs3746444 are associated with an increased ESCC risk in a Chinese population.

Authors

Shen, F; Chen, J; Guo, S; Zhou, Y; Zheng, Y; Yang, Y; Zhang, J; Wang, X; Wang, C; Zhao, D; Wang, M; Zhu, M; Fan, L; Xiang, J; Xia, Y; Wei, Q; Jin, L; Wang, J; Wang, M

MLA Citation

Shen, F, Chen, J, Guo, S, Zhou, Y, Zheng, Y, Yang, Y, Zhang, J, Wang, X, Wang, C, Zhao, D, Wang, M, Zhu, M, Fan, L, Xiang, J, Xia, Y, Wei, Q, Jin, L, Wang, J, and Wang, M. "Genetic variants in miR-196a2 and miR-499 are associated with susceptibility to esophageal squamous cell carcinoma in Chinese Han population." Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37.4 (April 2016): 4777-4784.

PMID

26518769

Source

epmc

Published In

Tumor Biology

Volume

37

Issue

4

Publish Date

2016

Start Page

4777

End Page

4784

DOI

10.1007/s13277-015-4268-3

Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42-0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43-0.94) and non-drinkers (OR = 0.79, 95% CI = 0.64-0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37-0.83) and non-drinker (adjusted OR = 0.75, 95% CI = 0.60-0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene-gene interactions among three AKT1 SNPs (P < 0.015). A three-AKT1 SNP haplotype (C-A-C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52-0.94). Multifactor dimensionality reduction analysis confirmed a high-order gene-environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene-environment interplay in ESCC carcinogenesis.

Authors

Zhu, J; Wang, M; He, J; Zhu, M; Wang, J-C; Jin, L; Wang, X-F; Yang, Y-J; Xiang, J-Q; Wei, Q

MLA Citation

Zhu, J, Wang, M, He, J, Zhu, M, Wang, J-C, Jin, L, Wang, X-F, Yang, Y-J, Xiang, J-Q, and Wei, Q. "Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population." Journal of Cellular and Molecular Medicine 20.4 (April 2016): 666-677.

PMID

26828791

Source

epmc

Published In

Journal of Cellular and Molecular Medicine

Volume

20

Issue

4

Publish Date

2016

Start Page

666

End Page

677

DOI

10.1111/jcmm.12750

Tobacco smoke and alcohol use play important roles in the etiology of squamous cell carcinoma of the head and neck (SCCHN). Smoking causes DNA damage, including double-strand DNA breaks (DSBs), that leads to carcinogenesis. To test the hypothesis that suboptimal DSB repair capacity is associated with risk of SCCHN, we applied a flow cytometry-based method to detect the DSB repair phenotype first in four EBV-immortalized human lymphoblastoid cell lines and then in human peripheral blood T-lymphocytes (PBTLs). With this blood-based laboratory assay, we conducted a pilot case-control study of 100 patients with newly diagnosed, previously untreated SCCHN and 124 cancer-free controls of non-Hispanic whites. We found that the mean DSB repair capacity level was significantly lower in cases (42.1%) than that in controls (54.4%) (P<0.001). When we used the median DSB repair capacity level in the controls as the cutoff value for calculating the odds ratios (ORs) with adjustment for age, sex, smoking and drinking status, the cases were more likely than the controls to have a reduced DSB repair capacity (adjusted OR=1.93; 95% confidence interval, CI=1.04-3.56, P=0.037), especially for those subjects who were ever drinkers (adjusted OR=2.73; 95% CI=1.17-6.35, P=0.020) and had oropharyngeal tumors (adjusted OR=2.17; 95% CI=1.06-4.45, P=0.035). In conclusion, these findings suggest that individuals with a reduced DSB repair capacity may be at an increased risk of developing SCCHN. Larger studies are warranted to confirm these preliminary findings.

Authors

Liu, Z; Liu, H; Gao, F; Dahlstrom, KR; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Liu, H, Gao, F, Dahlstrom, KR, Sturgis, EM, and Wei, Q. "Reduced DNA double-strand break repair capacity and risk of squamous cell carcinoma of the head and neck--A case-control study." DNA repair 40 (April 2016): 18-26.

PMID

26963119

Source

epmc

Published In

DNA Repair

Volume

40

Publish Date

2016

Start Page

18

End Page

26

DOI

10.1016/j.dnarep.2016.02.003

Single nucleotide polymorphisms (SNPs) in the vitamin D pathway genes have been implicated in cutaneous melanoma (CM) risk, but their role in CM disease-specific survival (DSS) remains obscure. We comprehensively analyzed the prognostic roles of 2669 common SNPs in the vitamin D pathway genes using data from a published genome-wide association study (GWAS) at The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated the SNPs of interest in another GWAS from the Nurses' Health Study and Health Professionals Follow-up Study. Among the 2669 SNPs, 203 were significantly associated with DSS in MDACC dataset (P < 0.05 and false-positive report probability < 0.2), of which 18 were the tag SNPs. In the replication, two of these 18 SNPs showed nominal significance: the VDBP rs12512631 T > C was associated with a better DSS [combined hazards ratio (HR) = 0.66]; and the same for RXRA rs7850212 C > A (combined HR = 0.38), which were further confirmed by the Fine and Gray competing-risks regression model. Further bioinformatics analyses indicated that these loci may modulate corresponding gene methylation status.

Authors

Yin, J; Liu, H; Yi, X; Wu, W; Amos, CI; Fang, S; Lee, JE; Han, J; Wei, Q

MLA Citation

Yin, J, Liu, H, Yi, X, Wu, W, Amos, CI, Fang, S, Lee, JE, Han, J, and Wei, Q. "Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival." Pigment cell & melanoma research 29.2 (March 2016): 176-185.

PMID

26575331

Source

epmc

Published In

Pigment Cell and Melanoma Research

Volume

29

Issue

2

Publish Date

2016

Start Page

176

End Page

185

DOI

10.1111/pcmr.12437

Published data on the association between the MUC1 rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. To derive a more precise estimation of the association, we conducted a large GCa study of 1,124 cases and 1,192 controls to confirm this association in an Eastern Chinese population. Our results showed that the G allele was strongly associated with a decreased GCa risk in the study population [GG vs. AA, odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.31-0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68-0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32-0.74]. These associations remained significant in subgroups of age, tumor site, drinking and smoking status. Moreover, this association was supported by an additional meta-analysis of published studies. In summary, these results suggest that the MUC1 rs4072037G allele may be a low-penetrating protection factor for GCa risk in Chinese populations.

Authors

Qiu, L-X; Hua, R-X; Cheng, L; He, J; Wang, M-Y; Zhou, F; Zhu, X-D; Sun, M-H; Zhou, X-Y; Li, J; Wang, Y-N; Yang, Y-J; Wang, J-C; Jin, L; Guo, W-J; Wei, Q-Y

MLA Citation

Qiu, L-X, Hua, R-X, Cheng, L, He, J, Wang, M-Y, Zhou, F, Zhu, X-D, Sun, M-H, Zhou, X-Y, Li, J, Wang, Y-N, Yang, Y-J, Wang, J-C, Jin, L, Guo, W-J, and Wei, Q-Y. "Genetic variant rs4072037 of MUC1 and gastric cancer risk in an Eastern Chinese population." Oncotarget 7.13 (March 2016): 15930-15936.

PMID

26910281

Source

epmc

Published In

Oncotarget

Volume

7

Issue

13

Publish Date

2016

Start Page

15930

End Page

15936

DOI

10.18632/oncotarget.7527

Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26,380 controls). A total of 44 significant SNPs with false discovery rate (FDR) ≤ 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P combined = 8.032 × 10(-6)) was with rs151606 within FGFR1OP. The rs151606 T>G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T>C (P combined = 9.589 × 10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P trend = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis.

Authors

Kang, X; Liu, H; Onaitis, MW; Liu, Z; Owzar, K; Han, Y; Su, L; Wei, Y; Hung, RJ; Brhane, Y; McLaughlin, J; Brennan, P; Bickeböller, H; Rosenberger, A; Houlston, RS; Caporaso, N; Landi, MT; Heinrich, J; Risch, A; Wu, X; Ye, Y; Christiani, DC; Amos, CI; Wei, Q; Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team,

MLA Citation

Kang, X, Liu, H, Onaitis, MW, Liu, Z, Owzar, K, Han, Y, Su, L, Wei, Y, Hung, RJ, Brhane, Y, McLaughlin, J, Brennan, P, Bickeböller, H, Rosenberger, A, Houlston, RS, Caporaso, N, Landi, MT, Heinrich, J, Risch, A, Wu, X, Ye, Y, Christiani, DC, Amos, CI, Wei, Q, and Transdisciplinary Research in Cancer of the Lung (TRICL) Research Team, . "Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls." Carcinogenesis 37.3 (March 2016): 280-289.

PMID

26905588

Source

epmc

Published In

Carcinogenesis

Volume

37

Issue

3

Publish Date

2016

Start Page

280

End Page

289

DOI

10.1093/carcin/bgw014

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that the rs2294008T variant genotypes were associated with an increased GCa risk in this study population (CT vs CC, OR=1.59, 95% CI=1.33-1.89 and CT+TT vs CC, OR=1.38, 95% CI=1.17-1.62). For SNP rs2976392, the variant A genotypes were also associated with an increased GCa risk (AG vs GG, OR=1.61, 95% CI=1.35-1.91 and AG+AA vs GG, OR=1.47, 95% CI=1.25-1.74). The results were further validated by a meta-analysis. In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population. However, large and well-designed studies are warranted to validate our findings.

Authors

Qiu, L-X; Cheng, L; He, J; Zhou, Z-R; Wang, M-Y; Zhou, F; Guo, W-J; Li, J; Sun, M-H; Zhou, X-Y; Wang, Y-N; Yang, Y-J; Wang, J-C; Jin, L; Zhu, X-D; Wei, Q-Y

MLA Citation

Qiu, L-X, Cheng, L, He, J, Zhou, Z-R, Wang, M-Y, Zhou, F, Guo, W-J, Li, J, Sun, M-H, Zhou, X-Y, Wang, Y-N, Yang, Y-J, Wang, J-C, Jin, L, Zhu, X-D, and Wei, Q-Y. "PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population." Oncotarget 7.8 (February 2, 2016): 9420-9428.

PMID

26848528

Source

epmc

Published In

Oncotarget

Volume

7

Issue

8

Publish Date

2016

Start Page

9420

End Page

9428

DOI

10.18632/oncotarget.7137

FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.

Authors

Sun, Y; Yu, W; Sturgis, EM; Peng, W; Lei, D; Wei, Q; Song, X; Li, G

MLA Citation

Sun, Y, Yu, W, Sturgis, EM, Peng, W, Lei, D, Wei, Q, Song, X, and Li, G. "Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck." BMC cancer 16 (February 2016): 70-.

PMID

26858129

Source

epmc

Published In

BMC Cancer

Volume

16

Publish Date

2016

Start Page

70

DOI

10.1186/s12885-016-2110-y

AKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings.

Authors

Wang, M-Y; He, J; Zhu, M-L; Teng, X-Y; Li, Q-X; Sun, M-H; Wang, X-F; Yang, Y-J; Wang, J-C; Jin, L; Wang, Y-N; Wei, Q-Y

MLA Citation

Wang, M-Y, He, J, Zhu, M-L, Teng, X-Y, Li, Q-X, Sun, M-H, Wang, X-F, Yang, Y-J, Wang, J-C, Jin, L, Wang, Y-N, and Wei, Q-Y. "A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population." Scientific reports 6 (January 28, 2016): 20008-.

PMID

26818920

Source

epmc

Published In

Scientific Reports

Volume

6

Publish Date

2016

Start Page

20008

DOI

10.1038/srep20008

Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries.We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients.The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues.yili@umich.edu.

Authors

He, K; Li, Y; Zhu, J; Liu, H; Lee, JE; Amos, CI; Hyslop, T; Jin, J; Lin, H; Wei, Q; Li, Y

MLA Citation

He, K, Li, Y, Zhu, J, Liu, H, Lee, JE, Amos, CI, Hyslop, T, Jin, J, Lin, H, Wei, Q, and Li, Y. "Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates." Bioinformatics (Oxford, England) 32.1 (January 2016): 50-57.

Website

http://hdl.handle.net/10161/10678

PMID

26382192

Source

epmc

Published In

Bioinformatics

Volume

32

Issue

1

Publish Date

2016

Start Page

50

End Page

57

DOI

10.1093/bioinformatics/btv517

Accumulative epidemiological evidence suggests that single nucleotide polymorphisms (SNPs) in genes involved in homologous recombination (HR) DNA repair pathway play an important role in glioma susceptibility. However, the effects of such SNPs on glioma risk remain unclear. We used a used a candidate pathway-based approach to elucidate the relationship between glioma risk and 12 putative functional SNPs in genes involved in the HR pathway. Genotyping was conducted on 771 histologically-confirmed glioma patients and 752 cancer-free controls from the Chinese Han population. Odds ratios (OR) were calculated both for each SNP individually and for grouped analyses, examining the effects of the numbers of adverse alleles on glioma risk, and evaluated their potential gene-gene interactions using the multifactor dimensionality reduction (MDR). In the single-locus analysis, two variants, the NBS1 rs1805794 (OR 1.42, 95% CI 1.15-1.76, P = 0.001), and RAD54L rs1048771 (OR 1.61, 95% CI 1.17-2.22, P = 0.002) were significantly associated with glioma risk. When we examined the joint effects of the risk-conferring alleles of these three SNPs, we found a significant trend indicating that the risk increases as the number of adverse alleles increase (P = 0.005). Moreover, the MDR analysis suggested a significant three-locus interaction model involving NBS1 rs1805794, MRE11 rs10831234, and ATM rs227062. These results suggested that these variants of the genes involved in the HR pathway may contribute to glioma susceptibility.

Authors

Zhang, H; Liu, Y; Zhou, K; Zhou, C; Zhou, R; Cheng, C; Wei, Q; Lu, D; Zhou, L

MLA Citation

Zhang, H, Liu, Y, Zhou, K, Zhou, C, Zhou, R, Cheng, C, Wei, Q, Lu, D, and Zhou, L. "Genetic variations in the homologous recombination repair pathway genes modify risk of glioma." Journal of neuro-oncology 126.1 (January 2016): 11-17.

PMID

26514363

Source

epmc

Published In

Journal of Neuro-Oncology

Volume

126

Issue

1

Publish Date

2016

Start Page

11

End Page

17

DOI

10.1007/s11060-015-1892-0

Telomere-related genes play an important role in carcinogenesis and progression of prostate cancer (PCa). It is not fully understood whether genetic variations in telomere-related genes are associated with development and progression in PCa patients.Six potentially functional single-nucleotide polymorphisms (SNPs) of three key telomere-related genes were evaluated in 1015 PCa cases and 1052 cancer-free controls, to test their associations with risk of PCa. Among 426 PCa patients who underwent radical prostatectomy (RP), the prognostic significance of the studied SNPs on biochemical recurrence (BCR) was also assessed using the Kaplan-Meier analysis and Cox proportional hazards regression model. The relative telomere lengths (RTLs) were measured in peripheral blood leukocytes using real-time PCR in the RP patients.TEP1 rs1760904 AG/AA genotypes were significantly associated with a decreased risk of PCa (odds ratio (OR): 0.77, 95% confidence interval (CI): 0.64-0.93, P=0.005) compared with the GG genotype. By using median RTL as a cutoff level, RP patients with TEP1 rs1760904 AG/AA genotypes tended to have a longer RTL than those with the GG genotype (OR: 1.55, 95% CI: 1.04-2.30, P=0.031). A significant interaction between TEP1 rs1713418 and age in modifying PCa risk was observed (P=0.005). After adjustment for clinicopathologic risk factors, the presence of heterozygotes or rare homozygotes of TEP1 rs1760904 and TNKS2 rs1539042 were associated with BCR in the RP cohorts (hazard ratio: 0.53, 95% CI: 0.36-0.79, P=0.002 and hazard ratio: 1.67, 95% CI: 1.07-2.48, P=0.017, respectively).These data suggest that genetic variations in the TEP1 gene may be biomarkers for risk of PCa and BCR after RP.

Authors

Gu, C; Li, Q; Zhu, Y; Qu, Y; Zhang, G; Wang, M; Yang, Y; Wang, J; Jin, L; Wei, Q; Ye, D

MLA Citation

Gu, C, Li, Q, Zhu, Y, Qu, Y, Zhang, G, Wang, M, Yang, Y, Wang, J, Jin, L, Wei, Q, and Ye, D. "Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence." Prostate cancer and prostatic diseases 18.4 (December 2015): 310-316.

Website

http://hdl.handle.net/10161/10664

PMID

26238235

Source

epmc

Published In

Prostate Cancer and Prostatic Diseases

Volume

18

Issue

4

Publish Date

2015

Start Page

310

End Page

316

DOI

10.1038/pcan.2015.27

Published data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs. TT, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.40-2.12; CC vs. TT, OR = 2.15, 95%CI = 1.70-2.71; CT/CC vs. TT, OR = 1.86, 95%CI = 1.53-2.26; CC vs.TT/CT, OR = 1.49, 95%CI = 1.24-1.79]. In addition, the association of C allele with an increased GCa risk was still significant in subgroups, when stratified by age, sex, tumor site, drinking and smoking status. Moreover, the findings in the present study were validated by our further meta-analysis. In summary, these results indicated that the C allele of PRKAA1 rs13361707 was a low-penetrate risk factor for GCa.

Authors

Qiu, L-X; He, J; Cheng, L; Zhou, F; Wang, M-Y; Sun, M-H; Zhou, X-Y; Li, J; Guo, W-J; Wang, Y-N; Yang, Y-J; Wang, J-C; Jin, L; Zhu, X-D; Wei, Q-Y

MLA Citation

Qiu, L-X, He, J, Cheng, L, Zhou, F, Wang, M-Y, Sun, M-H, Zhou, X-Y, Li, J, Guo, W-J, Wang, Y-N, Yang, Y-J, Wang, J-C, Jin, L, Zhu, X-D, and Wei, Q-Y. "Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population." Oncotarget 6.40 (December 2015): 42661-42666.

PMID

26485766

Source

epmc

Published In

Oncotarget

Volume

6

Issue

40

Publish Date

2015

Start Page

42661

End Page

42666

DOI

10.18632/oncotarget.6124

Authors

Zhang, H; Wang, M; Shi, T; Shen, L; Zhu, J; Sun, M; Deng, Y; Liang, L; Li, G; Wu, Y; Fan, M; Wei, Q; Zhang, Z

MLA Citation

Zhang, H, Wang, M, Shi, T, Shen, L, Zhu, J, Sun, M, Deng, Y, Liang, L, Li, G, Wu, Y, Fan, M, Wei, Q, and Zhang, Z. "Associations of Genetic Polymorphisms of PAI-1 and PAR-1 With Acute Normal Tissue Toxicity in Rectal Cancer Patients Treated With Pelvic Radiation Therapy." November 1, 2015.

Source

wos-lite

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

93

Issue

3

Publish Date

2015

Start Page

E511

End Page

E511

Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.

Authors

Zhang, F; Sturgis, EM; Sun, Y; Zhang, Y; Wei, Q; Zhang, C; Zheng, H; Li, G

MLA Citation

Zhang, F, Sturgis, EM, Sun, Y, Zhang, Y, Wei, Q, Zhang, C, Zheng, H, and Li, G. "Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy." International journal of cancer 137.10 (November 2015): 2454-2461.

Website

http://hdl.handle.net/10161/10674

PMID

25976983

Source

epmc

Published In

International Journal of Cancer

Volume

137

Issue

10

Publish Date

2015

Start Page

2454

End Page

2461

DOI

10.1002/ijc.29604

Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated.In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings.We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer.These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.

Authors

Wang, M-Y; Li, Q-X; He, J; Qiu, L-X; Wang, Y-N; Li, J; Sun, M-H; Wang, X-F; Yang, Y-J; Wang, J-C; Jin, L; Wei, Q-Y

MLA Citation

Wang, M-Y, Li, Q-X, He, J, Qiu, L-X, Wang, Y-N, Li, J, Sun, M-H, Wang, X-F, Yang, Y-J, Wang, J-C, Jin, L, and Wei, Q-Y. "Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population." Pharmacogenetics and genomics 25.11 (November 2015): 521-530.

PMID

26287940

Source

epmc

Published In

Pharmacogenetics and Genomics

Volume

25

Issue

11

Publish Date

2015

Start Page

521

End Page

530

DOI

10.1097/fpc.0000000000000163

Acute toxicity is the main dose-limiting factor in the chemoradiotherapy of rectal cancer patients and depends on several pro-inflammatory factors, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). It is unknown whether genetic factors, such as single-nucleotide polymorphisms (SNPs) in the IL-1, IL-6, and TNF genes, are also associated with acute toxicity in the process.We genotyped 5 potentially functional SNPs in these 3 genes (TNF rs1799964, TNF rs1800629, IL-6 rs1800796, and IL-1 rs1143623, IL-1 rs1143627) and estimated their associations with severe acute radiation injury (grade ≥2) in 356 rectal cancer patients.We found a predictive role of the TNF rs1799964 T variant allele in the development of acute injury (for CT vs CC: adjusted odds ratio [OR] = 4.718, 95% confidence interval [CI] = 1.152-19.328, P = 0.031; for TT vs CC: adjusted OR = 4.443, 95% CI = 1.123-17.581, P = 0.034). In the dominant model, for CT/TT vs CC, the adjusted OR = 4.132, 95% CI = 1.069-15.966, and P = 0.04.Our results suggested that genetic variants in the TNF gene may influence acute injury in rectal cancer patients treated with chemoradiotherapy and may be a predictor for personalized treatment. Additional larger and independent studies are needed to confirm our findings.

Authors

Zhang, H; Wang, M; Shi, T; Shen, L; Liang, L; Deng, Y; Li, G; Zhu, J; Wu, Y; Fan, M; Deng, W; Wei, Q; Zhang, Z

MLA Citation

Zhang, H, Wang, M, Shi, T, Shen, L, Liang, L, Deng, Y, Li, G, Zhu, J, Wu, Y, Fan, M, Deng, W, Wei, Q, and Zhang, Z. "TNF rs1799964 as a Predictive Factor of Acute Toxicities in Chinese Rectal Cancer Patients Treated With Chemoradiotherapy." Medicine 94.45 (November 2015): e1955-.

PMID

26559268

Source

epmc

Published In

Medicine

Volume

94

Issue

45

Publish Date

2015

Start Page

e1955

DOI

10.1097/md.0000000000001955

Esophageal cancer is one of the most aggressive cancers in the world, 70% of which are from China and esophageal squamous cell carcinoma (ESCC) is the major histopathological form (>90%). The single nucleotide polymorphisms (SNPs) in mature sequence of microRNA (miRNA) (mmSNPs) could cause the alteration of microRNA expression and contribute to the susceptibility of cancers. To evaluate the association between mmSNPs and ESCC, a case-control study including 773 patients with ESCC and 882 gender- and age-matched controls was carried out to investigate the association of five mmSNPs (miR-449b rs10061133, miR-4293 rs12220909, miR-608 rs4919510, miR-627 rs2620381, and miR-646 rs6513497) with ESCC susceptibility. As a result, two SNPs, miR-449b rs10061133 and miR-4293 rs12220909, were associated with decreased ESCC risk. For miR-449b rs10061133 A>G, individuals carrying GG genotype had an odds ratio (OR) of 0.77 (95% confidence interval (95% CI) 0.62-0.97) compared with individuals with AA genotype. In the recessive model, the GG genotype also showed a protective effect on ESCC (OR = 0.78, 95% CI 0.63-0.97). For miR-4293 rs12220909 G>C, the heterozygous genotype GC was associated with a decreased ESCC risk (OR = 0.77, 95% CI 0.61-0.97) compared with GG genotype. The C allele conferred 23% decrease in ESCC risk compared with the G allele in the allelic model (95% CI 0.63-0.93). In the dominant model, the GC/CC genotypes decreased the risk of ESCC (adjusted OR = 0.77, 95% CI 0.61-0.96). This study provides the first evidence that miR-449b rs10061133 and miR-4293 rs12220909 are associated with ESCC risk in Chinese population.

Authors

Zhang, P; Wang, J; Lu, T; Wang, X; Zheng, Y; Guo, S; Yang, Y; Wang, M; Kolluri, VK; Qiu, L; Shen, F; Fan, L; Li, J; Wang, Y; Wei, Q; Jin, L; Wang, J; Wang, M

MLA Citation

Zhang, P, Wang, J, Lu, T, Wang, X, Zheng, Y, Guo, S, Yang, Y, Wang, M, Kolluri, VK, Qiu, L, Shen, F, Fan, L, Li, J, Wang, Y, Wei, Q, Jin, L, Wang, J, and Wang, M. "miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population." Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36.11 (November 2015): 8789-8795.

PMID

26055141

Source

epmc

Published In

Tumor Biology

Volume

36

Issue

11

Publish Date

2015

Start Page

8789

End Page

8795

DOI

10.1007/s13277-015-3422-2

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.

Authors

Li, C; Gao, Z; Li, F; Li, X; Sun, Y; Wang, M; Li, D; Wang, R; Li, F; Fang, R; Pan, Y; Luo, X; He, J; Zheng, L; Xia, J; Qiu, L; He, J; Ye, T; Zhang, R; He, M; Zhu, M; Hu, H; Shi, T; Zhou, X; Sun, M; Tian, S; Zhou, Y; Wang, Q; Chen, L; Yin, G; Lu, J; Wu, R; Guo, G; Li, Y; Hu, X; Li, L; Asan, ; Wang, Q; Yin, Y; Feng, Q; Wang, B; Wang, H; Wang, M; Yang, X; Zhang, X; Yang, H; Jin, L; Wang, C-Y; Ji, H; Chen, H; Wang, J; Wei, Q

MLA Citation

Li, C, Gao, Z, Li, F, Li, X, Sun, Y, Wang, M, Li, D, Wang, R, Li, F, Fang, R, Pan, Y, Luo, X, He, J, Zheng, L, Xia, J, Qiu, L, He, J, Ye, T, Zhang, R, He, M, Zhu, M, Hu, H, Shi, T, Zhou, X, Sun, M, Tian, S, Zhou, Y, Wang, Q, Chen, L, Yin, G, Lu, J, Wu, R, Guo, G, Li, Y, Hu, X, Li, L, Asan, , Wang, Q, Yin, Y, Feng, Q, Wang, B, Wang, H, Wang, M, Yang, X, Zhang, X, Yang, H, Jin, L, Wang, C-Y, Ji, H, Chen, H, Wang, J, and Wei, Q. "Whole Exome Sequencing Identifies Frequent Somatic Mutations in Cell-Cell Adhesion Genes in Chinese Patients with Lung Squamous Cell Carcinoma." Scientific reports 5 (October 27, 2015): 14237-.

PMID

26503331

Source

epmc

Published In

Scientific Reports

Volume

5

Publish Date

2015

Start Page

14237

DOI

10.1038/srep14237

Genome-wide association studies (GWASs) have characterized 13 loci associated with melanoma, which only account for a small part of melanoma risk. To identify new genes with too small an effect to be detected individually but which collectively influence melanoma risk and/or show interactive effects, we used a two-step analysis strategy including pathway analysis of genome-wide SNP data, in a first step, and epistasis analysis within significant pathways, in a second step. Pathway analysis, using the gene-set enrichment analysis (GSEA) approach and the gene ontology (GO) database, was applied to the outcomes of MELARISK (3,976 subjects) and MDACC (2,827 subjects) GWASs. Cross-gene SNP-SNP interaction analysis within melanoma-associated GOs was performed using the INTERSNP software. Five GO categories were significantly enriched in genes associated with melanoma (false discovery rate ≤ 5% in both studies): response to light stimulus, regulation of mitotic cell cycle, induction of programmed cell death, cytokine activity and oxidative phosphorylation. Epistasis analysis, within each of the five significant GOs, showed significant evidence for interaction for one SNP pair at TERF1 and AFAP1L2 loci (pmeta-int  = 2.0 × 10(-7) , which met both the pathway and overall multiple-testing corrected thresholds that are equal to 9.8 × 10(-7) and 2.0 × 10(-7) , respectively) and suggestive evidence for another pair involving correlated SNPs at the same loci (pmeta-int  = 3.6 × 10(-6) ). This interaction has important biological relevance given the key role of TERF1 in telomere biology and the reported physical interaction between TERF1 and AFAP1L2 proteins. This finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development.

Authors

Brossard, M; Fang, S; Vaysse, A; Wei, Q; Chen, WV; Mohamdi, H; Maubec, E; Lavielle, N; Galan, P; Lathrop, M; Avril, M-F; Lee, JE; Amos, CI; Demenais, F

MLA Citation

Brossard, M, Fang, S, Vaysse, A, Wei, Q, Chen, WV, Mohamdi, H, Maubec, E, Lavielle, N, Galan, P, Lathrop, M, Avril, M-F, Lee, JE, Amos, CI, and Demenais, F. "Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk." International journal of cancer 137.8 (October 2015): 1901-1909.

Website

http://hdl.handle.net/10161/10671

PMID

25892537

Source

epmc

Published In

International Journal of Cancer

Volume

137

Issue

8

Publish Date

2015

Start Page

1901

End Page

1909

DOI

10.1002/ijc.29570

Circulating Epstein-Barr virus DNA is a predictor of disease recurrence in patients with nasopharyngeal carcinoma. Circulating human papillomavirus (HPV) DNA has been detected in the sera of some patients with HPV-positive squamous cell carcinoma of the oropharynx (OPC). The goal of the current study was to determine whether pretreatment serum HPV DNA is a useful biomarker for disease recurrence in patients with HPV-positive OPC.The study included patients with newly diagnosed, previously untreated OPC. Tumor HPV status was determined by polymerase chain reaction; serum HPV DNA was detected using real-time polymerase chain reaction. Differences in clinical characteristics between patients who were positive and negative for pretreatment serum HPV DNA were described using standard descriptive statistical methods. Kaplan-Meier curves were generated and log-rank tests were used to detect statistically significant differences in progression-free survival (PFS).A total of 262 patients were included. Patients with high N category and those with TNM stage IV disease were found to have higher rates of detectable pretreatment serum HPV DNA. Patients with HPV-positive tumors had better PFS than patients with HPV-negative tumors. Among patients with HPV-positive tumors, those who were negative for pretreatment serum HPV DNA had better PFS than those who were positive for pretreatment serum HPV DNA, but this result was not statistically significant.Pretreatment serum HPV DNA was associated with higher N category and overall disease stage. However, pretreatment serum HPV DNA does not appear to have clinical usefulness as a marker for disease recurrence among patients with OPC.

Authors

Dahlstrom, KR; Li, G; Hussey, CS; Vo, JT; Wei, Q; Zhao, C; Sturgis, EM

MLA Citation

Dahlstrom, KR, Li, G, Hussey, CS, Vo, JT, Wei, Q, Zhao, C, and Sturgis, EM. "Circulating human papillomavirus DNA as a marker for disease extent and recurrence among patients with oropharyngeal cancer." Cancer 121.19 (October 2015): 3455-3464.

PMID

26094818

Source

epmc

Published In

Cancer

Volume

121

Issue

19

Publish Date

2015

Start Page

3455

End Page

3464

DOI

10.1002/cncr.29538

The early detection of hepatocellular carcinoma (HCC) presents a challenge because of the lack of specific biomarkers. Serum/plasma microRNAs (miRNAs) can discriminate HCC patients from controls. We aimed to identify and evaluate HCC-associated plasma miRNAs originating from the liver as early biomarkers for detecting HCC. In this multicenter three-phase study, we first performed screening using both plasma (HCC before and after liver transplantation or liver hepatectomy) and tissue samples (HCC, para-carcinoma and cirrhotic tissues). Then, we evaluated the diagnostic potential of the miRNAs in two case-control studies (training and validation sets). Finally, we used two prospective cohorts to test the potential of the identified miRNAs for the early detection of HCC. During the screening phase, we identified ten miRNAs, eight of which (miR-20a-5p, miR-25-3p, miR-30a-5p, miR-92a-3p, miR-132-3p, miR-185-5p, miR-320a and miR-324-3p) were significantly overexpressed in the HBV-positive HCC patients compared with the HBV-positive cancer-free controls in both the training and validation sets, with a sensitivity of 0.866 and specificity of 0.646. Furthermore, we assessed the potential for early HCC detection of these eight newly identified miRNAs and three previously reported miRNAs (miR-192-5p, miR-21-5p and miR-375) in two prospective cohorts. Our meta-analysis revealed that four miRNAs (miR-20a-5p, miR-320a, miR-324-3p and miR-375) could be used as preclinical biomarkers (pmeta  < 0.05) for HCC. The expression profile of the eight-miRNA panel can be used to discriminate HCC patients from cancer-free controls, and the four-miRNA panel (alone or combined with AFP) could be a blood-based early detection biomarker for HCC screening.

Authors

Wen, Y; Han, J; Chen, J; Dong, J; Xia, Y; Liu, J; Jiang, Y; Dai, J; Lu, J; Jin, G; Han, J; Wei, Q; Shen, H; Sun, B; Hu, Z

MLA Citation

Wen, Y, Han, J, Chen, J, Dong, J, Xia, Y, Liu, J, Jiang, Y, Dai, J, Lu, J, Jin, G, Han, J, Wei, Q, Shen, H, Sun, B, and Hu, Z. "Plasma miRNAs as early biomarkers for detecting hepatocellular carcinoma." International journal of cancer 137.7 (October 2015): 1679-1690.

Website

http://hdl.handle.net/10161/10663

PMID

25845839

Source

epmc

Published In

International Journal of Cancer

Volume

137

Issue

7

Publish Date

2015

Start Page

1679

End Page

1690

DOI

10.1002/ijc.29544

Thymidylate synthase (TYMS) plays a crucial role in folate metabolism as well as DNA synthesis and repair. We hypothesized that functional polymorphisms in the 3' UTR of TYMS are associated with gastric cancer risk and survival. In the present study, we tested our hypothesis by genotyping three potentially functional (at miRNA binding sites) TYMS SNPs (rs16430 6bp del/ins, rs2790 A>G and rs1059394 C>T) in 379 gastric cancer patients and 431 cancer-free controls. Compared with the rs16430 6bp/6bp + 6bp/0bp genotypes, the 0bp/0bp genotype was associated with significantly increased gastric cancer risk (adjusted OR = 1.72, 95% CI = 1.15-2.58). Similarly, rs2790 GG and rs1059394 TT genotypes were also associated with significantly increased risk (adjusted OR = 2.52, 95% CI = 1.25-5.10 and adjusted OR = 1.57, 95% CI = 1.04-2.35, respectively), compared with AA + AG and CC + CT genotypes, respectively. In the haplotype analysis, the T-G-0bp haplotype was associated with significantly increased gastric cancer risk, compared with the C-A-6bp haplotype (adjusted OR = 1.34, 95% CI = 1.05-1.72). Survival analysis revealed that rs16430 0bp/0bp and rs1059394 TT genotypes were also associated with poor survival in gastric cancer patients who received chemotherapy treatment (adjusted HR = 1.61, 95% CI = 1.05-2.48 and adjusted HR = 1.59, 95% CI = 1.02-2.48, respectively). These results suggest that these three variants in the miRNA binding sites of TYMS may be associated with cancer risk and survival of gastric cancer patients. Larger population studies are warranted to verify these findings.

Authors

Shen, R; Liu, H; Wen, J; Liu, Z; Wang, L-E; Wang, Q; Tan, D; Ajani, JA; Wei, Q

MLA Citation

Shen, R, Liu, H, Wen, J, Liu, Z, Wang, L-E, Wang, Q, Tan, D, Ajani, JA, and Wei, Q. "Genetic polymorphisms in the microRNA binding-sites of the thymidylate synthase gene predict risk and survival in gastric cancer." Molecular carcinogenesis 54.9 (September 2015): 880-888.

PMID

24756984

Source

epmc

Published In

Molecular Carcinogenesis

Volume

54

Issue

9

Publish Date

2015

Start Page

880

End Page

888

DOI

10.1002/mc.22160

Platinum agents can cause the formation of DNA adducts and induce apoptosis to eliminate tumor cells. The aim of the present study was to investigate the influence of genetic variants of MDM2 on chemotherapy-related toxicities and clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC).We recruited 663 patients with advanced NSCLC who had been treated with first-line platinum-based chemotherapy. Five tagging single nucleotide polymorphisms (SNPs) in MDM2 were genotyped in these patients. The associations of these SNPs with clinical toxicities and outcomes were evaluated using logistic regression and Cox regression analyses.Two SNPs (rs1470383 and rs1690924) showed significant associations with chemotherapy-related toxicities (ie, overall, hematologic, and gastrointestinal toxicity). Compared with the wild genotype AA carriers, patients with the GG genotype of rs1470383 had an increased risk of overall toxicity (odds ratio [OR], 3.28; 95% confidence interval [CI], 1.34-8.02; P = .009) and hematologic toxicity (OR, 4.10; 95% CI, 1.73-9.71; P = .001). Likewise, patients with the AG genotype of rs1690924 showed more sensitivity to gastrointestinal toxicity than did those with the wild-type homozygote GG (OR, 2.32; 95% CI, 1.30-4.14; P = .004). Stratified survival analysis revealed significant associations between rs1470383 genotypes and overall survival in patients without overall or hematologic toxicity (P = .007 and P = .0009, respectively).The results of our study suggest that SNPs in MDM2 might be used to predict the toxicities of platinum-based chemotherapy and overall survival in patients with advanced NSCLC. Additional validations of the association are warranted.

Authors

Qian, J; Liu, H; Gu, S; Wu, Q; Zhao, X; Wu, W; Wang, H; Wang, J; Chen, H; Zhang, W; Wei, Q; Jin, L; Lu, D

MLA Citation

Qian, J, Liu, H, Gu, S, Wu, Q, Zhao, X, Wu, W, Wang, H, Wang, J, Chen, H, Zhang, W, Wei, Q, Jin, L, and Lu, D. "Genetic Variants of the MDM2 Gene Are Predictive of Treatment-Related Toxicities and Overall Survival in Patients With Advanced NSCLC." Clinical lung cancer 16.5 (September 2015): e37-e53.

Website

http://hdl.handle.net/10161/10677

PMID

25818095

Source

epmc

Published In

Clinical lung cancer

Volume

16

Issue

5

Publish Date

2015

Start Page

e37

End Page

e53

DOI

10.1016/j.cllc.2015.02.001

Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.

Authors

Fang, S; Wang, Y; Chun, YS; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Reveille, JD; Chen, W; Sui, D; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE

MLA Citation

Fang, S, Wang, Y, Chun, YS, Liu, H, Ross, MI, Gershenwald, JE, Cormier, JN, Royal, RE, Lucci, A, Schacherer, CW, Reveille, JD, Chen, W, Sui, D, Bassett, RL, Wang, L-E, Wei, Q, Amos, CI, and Lee, JE. "Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes." The Journal of investigative dermatology 135.9 (September 2015): 2266-2272.

Website

http://hdl.handle.net/10161/10676

PMID

25848976

Source

epmc

Published In

Journal of Investigative Dermatology

Volume

135

Issue

9

Publish Date

2015

Start Page

2266

End Page

2272

DOI

10.1038/jid.2015.138

The kinesin-like factor 1 B (KIF1B) gene plays an important role in the process of apoptosis and the transformation and progression of malignant cells. Genetic variations in KIF1B may contribute to risk of epithelial ovarian cancer (EOC). In this study of 1,324 EOC patients and 1,386 cancer-free female controls, we investigated associations between two potentially functional single nucleotide polymorphisms in KIF1B and EOC risk by the conditional logistic regression analysis. General linear regression model was used to evaluate the correlation between the number of variant alleles and KIF1B mRNA expression levels. We found that the rs17401966 variant AG/GG genotypes were significantly associated with a decreased risk of EOC (adjusted odds ratio (OR) = 0.81, 95 % confidence interval (CI) = 0.68-0.97), compared with the AA genotype, but no associations were observed for rs1002076. Women who carried both rs17401966 AG/GG and rs1002076 AG/AA genotypes of KIF1B had a 0.82-fold decreased risk (adjusted 95 % CI = 0.69-0.97), compared with others. Additionally, there was no evidence of possible interactions between about-mentioned co-variants. Further genotype-phenotype correlation analysis indicated that the number of rs17401966 variant G allele was significantly associated with KIF1B mRNA expression levels (P for GLM = 0.003 and 0.001 in all and Chinese subjects, respectively), with GG carriers having the lowest level of KIF1B mRNA expression. Taken together, the rs17401966 polymorphism likely regulates KIF1B mRNA expression and thus may be associated with EOC risk in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.

Authors

Shi, T-Y; Jiang, Z; Jiang, R; Yin, S; Wang, M-Y; Yu, K-D; Shao, Z-M; Sun, M-H; Zang, R; Wei, Q

MLA Citation

Shi, T-Y, Jiang, Z, Jiang, R, Yin, S, Wang, M-Y, Yu, K-D, Shao, Z-M, Sun, M-H, Zang, R, and Wei, Q. "Polymorphisms in the kinesin-like factor 1 B gene and risk of epithelial ovarian cancer in Eastern Chinese women." Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 36.9 (September 2015): 6919-6927.

Website

http://hdl.handle.net/10161/10672

PMID

25854172

Source

epmc

Published In

Tumor Biology

Volume

36

Issue

9

Publish Date

2015

Start Page

6919

End Page

6927

DOI

10.1007/s13277-015-3394-2

Patients with oropharyngeal cancer (OPC) have distinct risk factor profiles reflected in the human papillomavirus (HPV) status of their tumor, and these profiles may also be influenced by factors related to socioeconomic status (SES). The goal of this study was to describe the socioeconomic characteristics of a large cohort of patients with OPC according to HPV status, smoking status, and sexual behavior.Patients with OPC prospectively provided information about their smoking and alcohol use, socioeconomic characteristics, and sexual behaviors. HPV status was determined by a composite of immunohistochemistry for p16 expression, HPV in situ hybridization, and PCR assay in 356 patients. Standard descriptive statistics and logistic regression were used to compare socioeconomic characteristics between patient subgroups.Patients with HPV-positive OPC had higher levels of education, income, and overall SES. Among patients with HPV-positive OPC, never/light smokers had more than 5 times the odds of having at least a bachelor's degree and being in the highest level of SES compared with smokers. Patients with HPV-positive OPC and those with higher levels of education and SES had higher numbers of lifetime any and oral sex partners, although not all of these differences were significant.Socioeconomic differences among subgroups of OPC patients have implications for OPC prevention efforts, including tobacco cessation, behavior modification, and vaccination programs.

Authors

Dahlstrom, KR; Bell, D; Hanby, D; Li, G; Wang, L-E; Wei, Q; Williams, MD; Sturgis, EM

MLA Citation

Dahlstrom, KR, Bell, D, Hanby, D, Li, G, Wang, L-E, Wei, Q, Williams, MD, and Sturgis, EM. "Socioeconomic characteristics of patients with oropharyngeal carcinoma according to tumor HPV status, patient smoking status, and sexual behavior." Oral oncology 51.9 (September 2015): 832-838.

PMID

26120093

Source

epmc

Published In

Oral Oncology

Volume

51

Issue

9

Publish Date

2015

Start Page

832

End Page

838

DOI

10.1016/j.oraloncology.2015.06.005

© 2015 UICC. Cutaneous melanoma (CM) is the most lethal form of skin cancers. The Hippo pathway controls cell migration, development and sizes of the organs in diverse species, and deregulation of this pathway may affect CM progression and prognosis. Therefore, we hypothesized that genetic variants of Hippo pathway genes might predict survival of CM patients. We used the genotyping data of 1,115 common single nucleotide polymorphisms (SNPs) in the 12 pathway core genes (i.e., MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3 and TEAD4) from the dataset of our previously published CM genome-wide association study and comprehensively analyzed their associations with CM-specific survival (CSS) in 858 CM patients by using the Kaplan-Meier analyses and Cox proportional hazards regression models. We found a predictive role of YAP1 rs11225163 CC, TEAD1 rs7944031 AG+GG and TEAD4 rs1990330 CA+AA in the prognosis of CM. In addition, patients with an increasing number of unfavorable genotypes (NUG) had a markedly increased risk of death. After incorporating NUG in the model with clinical variables, the new model showed a significantly improved discriminatory ability to classify CSS (AUC increased from 82.03% to 84.56%). Our findings suggest that genetic variants of Hippo pathway genes, particularly YAP1 rs11225163, TEAD1 rs7944031 and TEAD4 rs1990330, may independently or jointly modulate survival of CM patients. Additional large, prospective studies are needed to validate these findings.

Authors

Yuan, H; Liu, H; Liu, Z; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q

MLA Citation

Yuan, H, Liu, H, Liu, Z, Zhu, D, Amos, CI, Fang, S, Lee, JE, and Wei, Q. "Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival." International Journal of Cancer 137.3 (August 1, 2015): 638-645.

Source

scopus

Published In

International Journal of Cancer

Volume

137

Issue

3

Publish Date

2015

Start Page

638

End Page

645

DOI

10.1002/ijc.29429

The atypical protein kinase C (aPKCι), encoded by the PRKCI gene, has been recently found to be a unique human oncoprotein, compared with some other diverse PKC isozymes. Genetic variations in PRKCI have also been reported to be associated with prostate cancer (PCa) risk in Caucasian populations, but no similar studies have been reported for Chinese populations. We genotyped two well-described PRKCI single nucleotide polymorphisms (SNPs) rs546950 and rs4955720 in 1015 PCa patients and 1044 cancer-free controls of Eastern Chinese men. SNPs in the vicinity of those two variants of PRKCI were evaluated using the in silico analysis. Logistic regression was then used to estimate their associations with and interactions in PCa risk. Although no significant main effects were found for the two tested SNPs in the single locus analysis, individuals carrying homozygote wide-type form of these two SNPs had slightly reduced PCa risk (adjusted OR = 0.63, 95% CI = 0.40-0.99, P = 0.045), compared with those carrying any of heterozygous or homozygous variant genotypes. Our results indicated that the two PRKCI SNPs were jointly associated with PCa risk in an Eastern Chinese population. Larger studies with multiethnic groups are warranted to confirm these findings and to explore the role of PRKCI SNPs in the etiology of PCa.

Authors

Li, Q; Gu, C; Zhu, Y; Wang, M; Yang, Y; Wang, J; Jin, L; Zhu, M-L; Shi, T-Y; He, J; Ye, D; Wei, Q

MLA Citation

Li, Q, Gu, C, Zhu, Y, Wang, M, Yang, Y, Wang, J, Jin, L, Zhu, M-L, Shi, T-Y, He, J, Ye, D, and Wei, Q. "Two novel PRKCI polymorphisms and prostate cancer risk in an Eastern Chinese Han population." Molecular carcinogenesis 54.8 (August 2015): 632-641.

PMID

24510606

Source

epmc

Published In

Molecular Carcinogenesis

Volume

54

Issue

8

Publish Date

2015

Start Page

632

End Page

641

DOI

10.1002/mc.22130

Cutaneous melanoma (CM) is the most lethal form of skin cancers. The Hippo pathway controls cell migration, development and sizes of the organs in diverse species, and deregulation of this pathway may affect CM progression and prognosis. Therefore, we hypothesized that genetic variants of Hippo pathway genes might predict survival of CM patients. We used the genotyping data of 1,115 common single nucleotide polymorphisms (SNPs) in the 12 pathway core genes (i.e., MST1, MST2, SAV1, LATS1, LATS2, MOB1A, MOB1B, YAP1, TEAD1, TEAD2, TEAD3 and TEAD4) from the dataset of our previously published CM genome-wide association study and comprehensively analyzed their associations with CM-specific survival (CSS) in 858 CM patients by using the Kaplan-Meier analyses and Cox proportional hazards regression models. We found a predictive role of YAP1 rs11225163 CC, TEAD1 rs7944031 AG+GG and TEAD4 rs1990330 CA+AA in the prognosis of CM. In addition, patients with an increasing number of unfavorable genotypes (NUG) had a markedly increased risk of death. After incorporating NUG in the model with clinical variables, the new model showed a significantly improved discriminatory ability to classify CSS (AUC increased from 82.03% to 84.56%). Our findings suggest that genetic variants of Hippo pathway genes, particularly YAP1 rs11225163, TEAD1 rs7944031 and TEAD4 rs1990330, may independently or jointly modulate survival of CM patients. Additional large, prospective studies are needed to validate these findings.

Authors

Yuan, H; Liu, H; Liu, Z; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q

MLA Citation

Yuan, H, Liu, H, Liu, Z, Zhu, D, Amos, CI, Fang, S, Lee, JE, and Wei, Q. "Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival." International journal of cancer 137.3 (August 2015): 638-645.

PMID

25628125

Source

epmc

Published In

International Journal of Cancer

Volume

137

Issue

3

Publish Date

2015

Start Page

638

End Page

645

DOI

10.1002/ijc.29429

The Notch signaling pathway is constitutively activated in human cutaneous melanoma to promote growth and aggressive metastatic potential of primary melanoma cells. Therefore, genetic variants in Notch pathway genes may affect the prognosis of cutaneous melanoma patients.We identified 6,256 SNPs in 48 Notch genes in 858 cutaneous melanoma patients included in a previously published cutaneous melanoma genome-wide association study dataset. Multivariate and stepwise Cox proportional hazards regression and false-positive report probability corrections were performed to evaluate associations between putative functional SNPs and cutaneous melanoma disease-specific survival. Receiver operating characteristic curve was constructed, and area under the curve was used to assess the classification performance of the model.Four putative functional SNPs of Notch pathway genes had independent and joint predictive roles in survival of cutaneous melanoma patients. The most significant variant was NCOR2 rs2342924 T>C (adjusted HR, 2.71; 95% confidence interval, 1.73-4.23; Ptrend = 9.62 × 10(-7)), followed by NCSTN rs1124379 G>A, NCOR2 rs10846684 G>A, and MAML2 rs7953425 G>A (Ptrend = 0.005, 0.005, and 0.013, respectively). The receiver operating characteristic analysis revealed that area under the curve was significantly increased after adding the combined unfavorable genotype score to the model containing the known clinicopathologic factors.Our results suggest that SNPs in Notch pathway genes may be predictors of cutaneous melanoma disease-specific survival.Our discovery offers a translational potential for using genetic variants in Notch pathway genes as a genotype score of biomarkers for developing an improved prognostic assessment and personalized management of cutaneous melanoma patients.

Authors

Zhang, W; Liu, H; Liu, Z; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q

MLA Citation

Zhang, W, Liu, H, Liu, Z, Zhu, D, Amos, CI, Fang, S, Lee, JE, and Wei, Q. "Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 24.7 (July 2015): 1101-1110.

Website

http://hdl.handle.net/10161/10668

PMID

25953768

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

24

Issue

7

Publish Date

2015

Start Page

1101

End Page

1110

DOI

10.1158/1055-9965.epi-14-1380-t

Genetic polymorphisms in the 3' untranslated regions (3' UTRs) targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3' UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity and defense against infection. Thus, we hypothesised that the rs3783553 polymorphism affects individual susceptibility to human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC).We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumour HPV16 DNA and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations.We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del+Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to those patients with Ins/Del+Ins/Ins genotypes. Additionally, functional relevance of this variant was characterised to explore the genotype-phenotype correlation.These results suggest that IL-1α 3' UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.

Authors

Zhang, Y; Sturgis, EM; Sun, Y; Sun, C; Wei, Q; Huang, Z; Li, G

MLA Citation

Zhang, Y, Sturgis, EM, Sun, Y, Sun, C, Wei, Q, Huang, Z, and Li, G. "A functional variant at miRNA-122 binding site in IL-1α 3' UTR predicts risk and HPV-positive tumours of oropharyngeal cancer." European journal of cancer (Oxford, England : 1990) 51.11 (July 2015): 1415-1423.

PMID

25981582

Source

epmc

Published In

European Journal of Cancer

Volume

51

Issue

11

Publish Date

2015

Start Page

1415

End Page

1423

DOI

10.1016/j.ejca.2015.04.016

Antibodies (Abs) to the HPV16 proteome increase risk for HPV-associated OPC (HPVOPC). The goal of this study was to investigate the association of a panel of HPV16 Abs with risk for OPC as well as the association of these Abs with tumor HPV and smoking status among patients with OPC.IgG Abs to the HPV16 antigens E1, E2, E4, E5, E6, E7, L1, L2 were quantified using a programmable ELISA assay. Sera were obtained from 258 OPC patients at diagnosis and 250 healthy controls. HPV16 tumor status was measured by PCR for 137 cases. Multivariable logistic regression was used to calculate odds ratios for the association of HPV16 Abs with risk for OPC.HPV16 E1, E2, E4, E5, E6, E7 and L1-specific IgG levels were elevated in OPC patients compared to healthy controls (p<0.05). After multivariable adjustment, Ab positivity for NE2, CE2, E6, and/or E7 was associated with OPC risk (OR [95% CI], 249.1 [99.3-624.9]). Among patients with OPC, Ab positivity for these antigens was associated with tumor HPV status, especially among never or light smokers (OR [95% CI], 6.5 [2.1-20.1] and OR [95% CI], 17.5 [4.0-77.2], respectively).Antibodies to HPV16 proteins are associated with increased risk for HPVOPC. Among patients with OPC, HPV16 Abs are associated with tumor HPV status, in particular among HPV positive patients with no or little smoking history.

Authors

Anderson, KS; Dahlstrom, KR; Cheng, JN; Alam, R; Li, G; Wei, Q; Gross, ND; Chowell, D; Posner, M; Sturgis, EM

MLA Citation

Anderson, KS, Dahlstrom, KR, Cheng, JN, Alam, R, Li, G, Wei, Q, Gross, ND, Chowell, D, Posner, M, and Sturgis, EM. "HPV16 antibodies as risk factors for oropharyngeal cancer and their association with tumor HPV and smoking status." Oral oncology 51.7 (July 2015): 662-667.

Website

http://hdl.handle.net/10161/10670

PMID

25957822

Source

epmc

Published In

Oral Oncology

Volume

51

Issue

7

Publish Date

2015

Start Page

662

End Page

667

DOI

10.1016/j.oraloncology.2015.04.011

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC + CC genotypes were associated with significantly increased GC risk (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies.

Authors

Wang, Q; Liu, H; Xiong, H; Liu, Z; Wang, L-E; Qian, J; Muddasani, R; Lu, V; Tan, D; Ajani, JA; Wei, Q

MLA Citation

Wang, Q, Liu, H, Xiong, H, Liu, Z, Wang, L-E, Qian, J, Muddasani, R, Lu, V, Tan, D, Ajani, JA, and Wei, Q. "Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer." Molecular carcinogenesis 54.6 (June 2015): 449-458.

PMID

24302553

Source

epmc

Published In

Molecular Carcinogenesis

Volume

54

Issue

6

Publish Date

2015

Start Page

449

End Page

458

DOI

10.1002/mc.22113

Authors

Zhang, M; Qureshi, AA; Fortner, RT; Hankinson, SE; Wei, Q; Wang, L-E; Eliassen, AH; Willett, WC; Hunter, DJ; Han, J

MLA Citation

Zhang, M, Qureshi, AA, Fortner, RT, Hankinson, SE, Wei, Q, Wang, L-E, Eliassen, AH, Willett, WC, Hunter, DJ, and Han, J. "Teenage acne and cancer risk in US women: A prospective cohort study." Cancer 121.10 (May 15, 2015): 1681-1687.

Source

crossref

Published In

Cancer

Volume

121

Issue

10

Publish Date

2015

Start Page

1681

End Page

1687

DOI

10.1002/cncr.29216

Acne reflects hormone imbalance and is a key component of several systemic diseases. We hypothesized that diagnosis of acne as a teenager might predict subsequent risk of hormone-related cancers.We followed 99,128 female nurses in the Nurses' Health Study II cohort for 20 years (1989-2009) and used Cox proportional hazards models to estimate the hazard ratios (HRs) of 8 specific cancers (breast, thyroid, colorectal, ovarian, cervical, and endometrial cancers, melanoma, and non-Hodgkin lymphoma) for women with a history of severe teenage acne.After thoroughly adjusting for the previously known risk factors for each cancer, we found that among women with a history of severe teenage acne, the relative risk increased, with a multivariable-adjusted HR of 1.44 (95% confidence interval [CI], 1.03-2.01) for melanoma. We replicated this association in an independent melanoma case-control study of 930 cases and 1026 controls (multivariable-adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). We also found that in both studies the individuals with teenage acne were more likely to have moles (52.7% vs 50.1%, P < .001 in the cohort study; and 55.2% vs 45.1%, P = .004 in the case-control study).Our findings suggest that a history of teenage acne might be a novel risk factor for melanoma independent from the known factors, which supports a need for continued investigation of these relationships.

Authors

Zhang, M; Qureshi, AA; Fortner, RT; Hankinson, SE; Wei, Q; Wang, L-E; Eliassen, AH; Willett, WC; Hunter, DJ; Han, J

MLA Citation

Zhang, M, Qureshi, AA, Fortner, RT, Hankinson, SE, Wei, Q, Wang, L-E, Eliassen, AH, Willett, WC, Hunter, DJ, and Han, J. "Teenage acne and cancer risk in US women: A prospective cohort study." Cancer 121.10 (May 2015): 1681-1687.

PMID

25572604

Source

epmc

Published In

Cancer

Volume

121

Issue

10

Publish Date

2015

Start Page

1681

End Page

1687

DOI

10.1002/cncr.29216

Cytokines such as Interleukin (IL)-12p70 ("IL-12") and IL-23 can influence tumor progression. We tested the hypothesis that blood levels of IL-12p40, the common subunit of both cytokines, are associated with melanoma progression. Blood from 2,048 white melanoma patients were collected at a single institution between March 1998 and March 2011. Plasma levels of IL-12p40 were determined for 573 patients (discovery), 249 patients (Validation 1) and 244 patients (Validation 2). Per 10-unit change of IL-12p40 level was used to investigate associations with melanoma patient outcome among all patients or among patients with early or advanced stage. Among stage I/II melanoma patients in the pooled data set, after adjustment for sex, age, stage and blood draw time from diagnosis, elevated IL-12p40 was associated with melanoma recurrence [hazard ratio (HR) = 1.04 per 10-unit increase in IL-12p40, 95% CI 1.02-1.06, p = 8.48 × 10(-5) ]; Elevated IL-12p40 was also associated with a poorer melanoma specific survival (HR = 1.06, 95% CI 1.03-1.09, p = 3.35 × 10(-5) ) and overall survival (HR = 1.05, 95% CI 1.03-1.08, p = 8.78×10(-7) ) in multivariate analysis. Among stage III/IV melanoma patients in the pooled data set, no significant association was detected between elevated IL-12p40 and overall survival, or with melanoma specific survival, with or without adjustment for the above covariates. Early stage melanoma patients with elevated IL-12p40 levels are more likely to develop disease recurrence and have a poorer survival. Further investigation with a larger sample size will be needed to determine the role of IL-12p40 in advanced stage melanoma patients.

Authors

Fang, S; Wang, Y; Chun, YS; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Reveille, JD; Sui, D; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE

MLA Citation

Fang, S, Wang, Y, Chun, YS, Liu, H, Ross, MI, Gershenwald, JE, Cormier, JN, Royal, RE, Lucci, A, Schacherer, CW, Reveille, JD, Sui, D, Bassett, RL, Wang, L-E, Wei, Q, Amos, CI, and Lee, JE. "The relationship between blood IL-12p40 level and melanoma progression." International journal of cancer 136.8 (April 2015): 1874-1880.

Website

http://hdl.handle.net/10161/10669

PMID

25196740

Source

epmc

Published In

International Journal of Cancer

Volume

136

Issue

8

Publish Date

2015

Start Page

1874

End Page

1880

DOI

10.1002/ijc.29182

To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival.Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests.Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression.CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma.

Authors

Fang, S; Wang, Y; Sui, D; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Gardner, JM; Reveille, JD; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE

MLA Citation

Fang, S, Wang, Y, Sui, D, Liu, H, Ross, MI, Gershenwald, JE, Cormier, JN, Royal, RE, Lucci, A, Schacherer, CW, Gardner, JM, Reveille, JD, Bassett, RL, Wang, L-E, Wei, Q, Amos, CI, and Lee, JE. "C-reactive protein as a marker of melanoma progression." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 33.12 (April 2015): 1389-1396.

PMID

25779565

Source

epmc

Published In

Journal of Clinical Oncology

Volume

33

Issue

12

Publish Date

2015

Start Page

1389

End Page

1396

DOI

10.1200/jco.2014.58.0209

Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤ 55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08-1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06-2.03, P = 0.022), never smokers (OR = 1.67, 95% CI = 1.23-2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01-2.05, P = 0.043), and estrogen receptor-positive patients (OR = 1.46, 95% CI = 1.11-1.92, P = 0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0 bp allele had a decrease in both luciferase activity by ∼ 70% and mRNA levels by ∼ 50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤ 55 yr. Further validation in large population-based or cohort studies is needed.

Authors

Guan, X; Liu, H; Ju, J; Li, Y; Li, P; Wang, L-E; Brewster, AM; Buchholz, TA; Arun, BK; Wei, Q; Liu, Z

MLA Citation

Guan, X, Liu, H, Ju, J, Li, Y, Li, P, Wang, L-E, Brewster, AM, Buchholz, TA, Arun, BK, Wei, Q, and Liu, Z. "Genetic variant rs16430 6bp > 0bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-Hispanic white women aged ≤ 55 years." Molecular carcinogenesis 54.4 (April 2015): 281-290.

PMID

24166930

Source

epmc

Published In

Molecular Carcinogenesis

Volume

54

Issue

4

Publish Date

2015

Start Page

281

End Page

290

DOI

10.1002/mc.22097

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Authors

Conway, DI; Brenner, DR; McMahon, AD; Macpherson, LMD; Agudo, A; Ahrens, W; Bosetti, C; Brenner, H; Castellsague, X; Chen, C; Curado, MP; Curioni, OA; Dal Maso, L; Daudt, AW; de Gois Filho, JF; D'Souza, G; Edefonti, V; Fabianova, E; Fernandez, L; Franceschi, S; Gillison, M; Hayes, RB; Healy, CM; Herrero, R; Holcatova, I; Jayaprakash, V; Kelsey, K; Kjaerheim, K; Koifman, S; La Vecchia, C; Lagiou, P; Lazarus, P; Levi, F; Lissowska, J; Luce, D; Macfarlane, TV; Mates, D; Matos, E; McClean, M et al.

MLA Citation

Conway, DI, Brenner, DR, McMahon, AD, Macpherson, LMD, Agudo, A, Ahrens, W, Bosetti, C, Brenner, H, Castellsague, X, Chen, C, Curado, MP, Curioni, OA, Dal Maso, L, Daudt, AW, de Gois Filho, JF, D'Souza, G, Edefonti, V, Fabianova, E, Fernandez, L, Franceschi, S, Gillison, M, Hayes, RB, Healy, CM, Herrero, R, Holcatova, I, Jayaprakash, V, Kelsey, K, Kjaerheim, K, Koifman, S, La Vecchia, C, Lagiou, P, Lazarus, P, Levi, F, Lissowska, J, Luce, D, Macfarlane, TV, Mates, D, Matos, E, and McClean, M et al. "Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries." International journal of cancer 136.5 (March 2015): 1125-1139.

PMID

24996155

Source

epmc

Published In

International Journal of Cancer

Volume

136

Issue

5

Publish Date

2015

Start Page

1125

End Page

1139

DOI

10.1002/ijc.29063

Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

Authors

Yin, J; Liu, H; Liu, Z; Wang, L-E; Chen, WV; Zhu, D; Amos, CI; Fang, S; Lee, JE; Wei, Q

MLA Citation

Yin, J, Liu, H, Liu, Z, Wang, L-E, Chen, WV, Zhu, D, Amos, CI, Fang, S, Lee, JE, and Wei, Q. "Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival." The Journal of investigative dermatology 135.2 (February 2015): 542-550.

PMID

25243787

Source

epmc

Published In

Journal of Investigative Dermatology

Volume

135

Issue

2

Publish Date

2015

Start Page

542

End Page

550

DOI

10.1038/jid.2014.416

Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients.We pooled data from 25 case-control studies and conducted separate analyses for adults ≤ 45 years old ('young adults', 2010 cases and 4042 controls) and >45 years old ('older adults', 17700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs).The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI=9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking=5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR=2.27 (95% CI=1.26, 4.10)], but not in the older adults [OR=1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2.41%, 5.80%) in older adults.Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.

Authors

Toporcov, TN; Znaor, A; Zhang, Z-F; Yu, G-P; Winn, DM; Wei, Q; Vilensky, M; Vaughan, T; Thomson, P; Talamini, R; Szeszenia-Dabrowska, N; Sturgis, EM; Smith, E; Shangina, O; Schwartz, SM; Schantz, S; Rudnai, P; Richiardi, L; Ramroth, H; Purdue, MP; Olshan, AF; Eluf-Neto, J; Muscat, J; Moyses, RA; Morgenstern, H; Menezes, A; McClean, M; Matsuo, K; Mates, D; Macfarlane, TV; Lissowska, J; Levi, F; Lazarus, P; La Vecchia, C; Lagiou, P; Koifman, S; Kjaerheim, K; Kelsey, K; Holcatova, I; Herrero, R et al.

MLA Citation

Toporcov, TN, Znaor, A, Zhang, Z-F, Yu, G-P, Winn, DM, Wei, Q, Vilensky, M, Vaughan, T, Thomson, P, Talamini, R, Szeszenia-Dabrowska, N, Sturgis, EM, Smith, E, Shangina, O, Schwartz, SM, Schantz, S, Rudnai, P, Richiardi, L, Ramroth, H, Purdue, MP, Olshan, AF, Eluf-Neto, J, Muscat, J, Moyses, RA, Morgenstern, H, Menezes, A, McClean, M, Matsuo, K, Mates, D, Macfarlane, TV, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Lagiou, P, Koifman, S, Kjaerheim, K, Kelsey, K, Holcatova, I, and Herrero, R et al. "Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium." International journal of epidemiology 44.1 (February 2015): 169-185.

PMID

25613428

Source

epmc

Published In

International Journal of Epidemiology

Volume

44

Issue

1

Publish Date

2015

Start Page

169

End Page

185

DOI

10.1093/ije/dyu255

Single nucleotide polymorphisms (SNPs) in the PI3K/PTEN/AKT/mTOR signaling pathway may contribute to carcinogenesis. We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk. We observed no association with ESCC risk for any of the selected SNPs. However, the combined analysis of these SNPs revealed that subjects with one-to-three risk genotypes had an increased ESCC risk. Stratified analysis by body mass index (BMI) found that ESCC risk was significantly associated with each of three mTOR SNPs among subjects with BMI < 25.0. Specifically, we found that subjects carrying ≥ 1 risk genotypes had significantly increased ESCC risk, particularly for males, ever-smokers, ever-drinkers, and those with age > 60, or BMI < 25.0. Moreover, three mTOR haplotypes were associated with an increase in ESCC risk. Our meta-analysis of mTOR rs2295080 and cancer risk provided further evidence that mTOR SNPs might modulate cancer susceptibility. In this population, such risk effects might be modified by other risk factors, highlighting the importance of gene-environment interaction in esophageal carcinogenesis. Additional, larger studies are warranted to validate our findings.

Authors

Zhu, J; Wang, M; Zhu, M; He, J; Wang, J-C; Jin, L; Wang, X-F; Xiang, J-Q; Wei, Q

MLA Citation

Zhu, J, Wang, M, Zhu, M, He, J, Wang, J-C, Jin, L, Wang, X-F, Xiang, J-Q, and Wei, Q. "Associations of PI3KR1 and mTOR polymorphisms with esophageal squamous cell carcinoma risk and gene-environment interactions in Eastern Chinese populations." Scientific reports 5 (January 2015): 8250-.

PMID

25654238

Source

epmc

Published In

Scientific Reports

Volume

5

Publish Date

2015

Start Page

8250

DOI

10.1038/srep08250

Polymorphisms in Caspase-7 (CASP7) may modulate the programmed cell death and thus contribute to cervical cancer risk. In this case-control study of 1,486 cervical cancer cases and 1,301 controls, we investigated associations between four potentially functional polymorphisms in CASP7 and cervical cancer risk and evaluated their locus-locus interaction effects on the risk. The genotype-phenotype correlation was performed by a generalized linear regression model. We found that the rs4353229 polymorphism was associated with cervical cancer risk (under a recessive model: crude OR = 1.20, 95% CI = 1.02-1.40). Compared with the TT genotype, the rs10787498GT genotype was associated with an increased cervical cancer risk (adjusted OR = 1.19, 95% CI = 1.00-1.41). Combination analysis showed that subjects with four putative risk genotypes had a 1.54-fold increased cancer risk, compared with those who carried three or less putative risk genotypes. We also observed significant locus-locus joint effects on the risk, which may be mediated by the polymorphisms regulating CASP7 mRNA expression. Subsequent multifactor dimensionality reduction and classification and regression tree analyses indicated that the CASP7 genotypes might have a locus-locus interaction effect that modulated cervical cancer risk. Out data suggest that CASP7 polymorphisms may interact to modify cervical cancer risk by a possible mechanism of regulating CASP7 mRNA expression.

Authors

Shi, T-Y; He, J; Wang, M-Y; Zhu, M-L; Yu, K-D; Shao, Z-M; Sun, M-H; Wu, X; Cheng, X; Wei, Q

MLA Citation

Shi, T-Y, He, J, Wang, M-Y, Zhu, M-L, Yu, K-D, Shao, Z-M, Sun, M-H, Wu, X, Cheng, X, and Wei, Q. "CASP7 variants modify susceptibility to cervical cancer in Chinese women." Scientific reports 5 (January 2015): 9225-.

PMID

25784056

Source

epmc

Published In

Scientific Reports

Volume

5

Publish Date

2015

Start Page

9225

DOI

10.1038/srep09225

Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (P<0.05), whereas the AG and GG genotypes of rs2227631 in PAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.

Authors

Zhang, H; Wang, M; Shi, T; Shen, L; Zhu, J; Sun, M; Deng, Y; Liang, L; Li, G; Wu, Y; Fan, M; Wei, Q; Zhang, Z

MLA Citation

Zhang, H, Wang, M, Shi, T, Shen, L, Zhu, J, Sun, M, Deng, Y, Liang, L, Li, G, Wu, Y, Fan, M, Wei, Q, and Zhang, Z. "Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy." OncoTargets and therapy 8 (January 2015): 2291-2301.

PMID

26347502

Source

epmc

Published In

OncoTargets and Therapy

Volume

8

Publish Date

2015

Start Page

2291

End Page

2301

DOI

10.2147/ott.s83723

© 2015 Elsevier Ltd. All rights reserved.Background: Genetic polymorphisms in the 3′ untranslated regions (3′ UTRs) targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behaviour of individual miRNAs. An insertion (Ins)/deletion (Del) polymorphism (rs3783553) in the 3′ UTR of IL-1α may disrupt a binding site for miRNA-122. IL-1α plays an important role in inflammation, immunity and defense against infection. Thus, we hypothesised that the rs3783553 polymorphism affects individual susceptibility to human papillomavirus (HPV)-associated oral squamous cell carcinoma (OSCC). Methods: We genotyped the rs3783553 polymorphism; and determined HPV16 L1 serology, tumour HPV16 DNA and serum IL-1α expression. Univariate/multivariable logistic regression models were used to calculate associations. Results: We found that HPV16 L1 seropositivity alone was associated with an increased risk of OSCC (Odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6), and the risk of HPV16-associated OSCC was modified by the rs3783553 polymorphism. Patients with both HPV16 L1 seropositivity and Del/Del genotype for the rs3783553 had the highest risk of OSCC when using patients with HPV16 L1 seronegativity and Ins/Del + Ins/Ins genotypes as a comparison group. Notably, that effect modification was particularly pronounced in several subgroups (e.g. SCCOP, never-smokers and never-drinkers). The patients with Del/Del genotype were approximately 3.0 times more likely to have HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) tumours compared to those patients with Ins/Del + Ins/Ins genotypes. Additionally, functional relevance of this variant was characterised to explore the genotype-phenotype correlation. Conclusion: These results suggest that IL-1α 3′ UTR rs3783553 polymorphism may be functional and influence susceptibility to HPV16-associated OSCC, particularly for SCCOP. Validation of our findings is warranted.

Authors

Zhang, Y; Sturgis, EM; Sun, Y; Sun, C; Wei, Q; Huang, Z; Li, G

MLA Citation

Zhang, Y, Sturgis, EM, Sun, Y, Sun, C, Wei, Q, Huang, Z, and Li, G. "A functional variant at miRNA-122 binding site in IL-1α 3′ UTR predicts risk and HPV-positive tumours of oropharyngeal cancer." European Journal of Cancer 51.11 (2015): 1415-1423.

Source

scival

Published In

European Journal of Cancer

Volume

51

Issue

11

Publish Date

2015

Start Page

1415

End Page

1423

DOI

10.1016/j.ejca.2015.04.016

Authors

Chen, K; Ma, H; Li, L; Zang, R; Wang, C; Song, F; Shi, T; Yu, D; Yang, M; Xue, W; Dai, J; Li, S; Zheng, H; Wu, C; Zhang, Y; Wu, X; Li, D; Xue, F; Li, H; Jiang, Z; Liu, J; Liu, Y; Li, P; Tan, W; Han, J; Jie, J; Hao, Q; Hu, Z; Lin, D; Ma, D; Jia, W; Shen, H; Wei, Q

MLA Citation

Chen, K, Ma, H, Li, L, Zang, R, Wang, C, Song, F, Shi, T, Yu, D, Yang, M, Xue, W, Dai, J, Li, S, Zheng, H, Wu, C, Zhang, Y, Wu, X, Li, D, Xue, F, Li, H, Jiang, Z, Liu, J, Liu, Y, Li, P, Tan, W, Han, J, Jie, J, Hao, Q, Hu, Z, Lin, D, Ma, D, Jia, W, Shen, H, and Wei, Q. "Corrigendum: Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women." Nature Communications 5 (December 17, 2014): 5828-5828.

Source

crossref

Published In

Nature Communications

Volume

5

Publish Date

2014

Start Page

5828

End Page

5828

DOI

10.1038/ncomms6828

XRCC4 plays a crucial role in the non-homologous end joining pathway that maintains genome stability. In this two-stage case-control study with 1,764 non-BRCA1/2 breast cancer patients and 1,623 cancer-free controls, we investigated the contribution of genetic variants of XRCC4 to breast cancer susceptibility in Chinese women. We identified a recessive missense variant, rs3734091 (c.739G>T, p.Ala247Ser), of XRCC4 that was significantly associated with an increased risk of breast cancer (odds ratio [OR] = 3.92, P = 0.007), particularly with the risk of developing triple-negative breast cancer (OR = 18.65, P < 0.0001). This p.Ala247Ser variant disturbed the nuclear localization of XRCC4 in cells homozygous for the rs3734091-T allele but not in heterozygous cells at both the cellular and tissue levels. In heterozygous cells, wild-type XRCC4 facilitated the nuclear localization of the XRCC4A247S mutant, thus compensating for the impaired localization of XRCC4A247S. This provided a biological mechanism by which rs3734091 conferred an increased susceptibility to non-BRCA1/2 breast cancer exclusively under a recessive model. Further functional analyses revealed that p.Ala247Ser impaired the DNA damage repair capacity and ultimately perturbed genomic stability. Taken together, our findings document the role of XRCC4 in non-BRCA1/2 breast cancer predisposition and reveal its underlying biological mechanism of action.

Authors

He, M; Hu, X; Chen, L; Cao, A-Y; Yu, K-D; Shi, T-Y; Kuang, X-Y; Shi, W-B; Ling, H; Li, S; Qiao, F; Yao, L; Wei, Q; Di, G-H; Shao, Z-M

MLA Citation

He, M, Hu, X, Chen, L, Cao, A-Y, Yu, K-D, Shi, T-Y, Kuang, X-Y, Shi, W-B, Ling, H, Li, S, Qiao, F, Yao, L, Wei, Q, Di, G-H, and Shao, Z-M. "A recessive variant of XRCC4 predisposes to non- BRCA1/2 breast cancer in chinese women and impairs the DNA damage response via dysregulated nuclear localization." Oncotarget 5.23 (December 2014): 12218-12232.

PMID

25360583

Source

epmc

Published In

Oncotarget

Volume

5

Issue

23

Publish Date

2014

Start Page

12218

End Page

12232

DOI

10.18632/oncotarget.2623

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological processes. We sought to investigate whether three serum miRNAs related to immunity or inflammation were associated with esophagitis induced by chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: We measured serum miR-155, miR-221 and miR-21, before and during week 1-2 of CRT for 101 NSCLC patients by real-time PCR. Associations between miRNA and severe radiation-induced esophageal toxicity (RIET) were analyzed by logistic regression. RESULTS: We found that patients with stage IIIB-IV disease, higher mean esophagus dose or esophageal V50 had higher rates of severe RIET. Furthermore, high levels of miR-155 and miR-221 at week 1-2 of CRT were also risk factors for severe RIET (miR-155: OR=1.53, 95% CI: 1.04-2.25, P=0.03; miR-221: OR=2.07, 95% CI: 1.17-3.64, P=0.012). In addition, the fold change of miR-221 was also predictive of severe RIET (OR=1.18, 95% CI: 1.02-1.37, P=0.026). However, pretreatment miRNAs was not predictive of severe RIET. CONCLUSIONS: High serum miR-155 and miR-221 during the first 2 weeks of CRT were associated with the development of severe RIET, suggesting that these miRNAs may be useful as an early surrogate for this form of toxicity.

Authors

Xu, T; Liao, Z; O'Reilly, MS; Levy, LB; Welsh, JW; Wang, L-E; Lin, SH; Komaki, R; Liu, Z; Wei, Q; Gomez, DR

MLA Citation

Xu, T, Liao, Z, O'Reilly, MS, Levy, LB, Welsh, JW, Wang, L-E, Lin, SH, Komaki, R, Liu, Z, Wei, Q, and Gomez, DR. "Serum inflammatory miRNAs predict radiation esophagitis in patients receiving definitive radiochemotherapy for non-small cell lung cancer." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 113.3 (December 2014): 379-384.

PMID

25466375

Source

epmc

Published In

Radiotherapy & Oncology

Volume

113

Issue

3

Publish Date

2014

Start Page

379

End Page

384

DOI

10.1016/j.radonc.2014.11.006

MicroRNAs (miRNA) play important roles in the regulation of eukaryotic gene expression and are involved in human carcinogenesis. Single-nucleotide polymorphisms (SNP) in miRNA sequence may alter miRNA functions in gene regulation, which, in turn, may affect cancer risk and disease progression.We conducted an analysis of associations of 142 miRNA SNPs with non-small cell lung cancer (NSCLC) survival using data from a genome-wide association study (GWAS) in a Caucasian population from the Massachusetts General Hospital (Boston, MA) including 452 early-stage and 526 late-stage NSCLC cases. Replication analyses were further performed in two external populations, one Caucasian cohort from The University of Texas MD Anderson Cancer Center (Houston, TX) and one Han Chinese cohort from Nanjing, China.We identified seven significant SNPs in the discovery set. Results from the independent Caucasian cohort demonstrated that the C allele of rs2042253 (hsa-miRNA-5197) was significantly associated with decreased risk for death among the patients with late-stage NSCLC (discovery set: HR, 0.80; P = 0.007; validation set: HR, 0.86; P = 0.035; combined analysis: HR, 0.87; P = 0.007).These findings provide evidence that some miRNA SNPs are associated with NSCLC survival and can be used as predictive biomarkers.This study provided an estimate of outcome probability for survival experience of patients with NSCLC, which demonstrates that genetic factors, as well as classic nongenetic factors, may be used to predict individual outcome.

Authors

Zhao, Y; Wei, Q; Hu, L; Chen, F; Hu, Z; Heist, RS; Su, L; Amos, CI; Shen, H; Christiani, DC

MLA Citation

Zhao, Y, Wei, Q, Hu, L, Chen, F, Hu, Z, Heist, RS, Su, L, Amos, CI, Shen, H, and Christiani, DC. "Polymorphisms in MicroRNAs are associated with survival in non-small cell lung cancer." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 23.11 (November 2014): 2503-2511.

PMID

25103824

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

23

Issue

11

Publish Date

2014

Start Page

2503

End Page

2511

DOI

10.1158/1055-9965.epi-14-0389

Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48-0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10⁻³). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.

Authors

Gu, C-Y; Li, Q-X; Zhu, Y; Wang, M-Y; Shi, T-Y; Yang, Y-Y; Wang, J-C; Jin, L; Wei, Q-Y; Ye, D-W

MLA Citation

Gu, C-Y, Li, Q-X, Zhu, Y, Wang, M-Y, Shi, T-Y, Yang, Y-Y, Wang, J-C, Jin, L, Wei, Q-Y, and Ye, D-W. "Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men." Asian journal of andrology 16.6 (November 2014): 878-883.

PMID

25038177

Source

epmc

Published In

Asian journal of andrology

Volume

16

Issue

6

Publish Date

2014

Start Page

878

End Page

883

DOI

10.4103/1008-682x.129939

To identify genetic markers for laryngeal squamous cell carcinoma (LSCC), we conducted a genome-wide association study (GWAS) on 993 individuals with LSCC (cases) and 1,995 cancer-free controls from Chinese populations. The most promising variants (association P < 1 × 10(-5)) were then replicated in 3 independent sets including 2,398 cases and 2,804 controls, among which we identified 3 new susceptibility loci at 11q12 (rs174549), 6p21 (rs2857595) and 12q24 (rs10492336). The minor alleles of each of these loci showed protective effects, with odds ratios (95% confidence intervals) of 0.73 (0.68-0.78; P = 1.00 × 10(-20)), 0.78 (0.72-0.84; P = 2.43 × 10(-15)) and 0.71 (0.65-0.77; P = 4.48 × 10(-14)), respectively. None of these variants showed an interaction with smoking or drinking. This is the first GWAS to our knowledge solely on LSCC, and the findings might advance understanding of the etiology of LSCC.

Authors

Wei, Q; Yu, D; Liu, M; Wang, M; Zhao, M; Liu, M; Jia, W; Ma, H; Fang, J; Xu, W; Chen, K; Xu, Z; Wang, J; Tian, L; Yuan, H; Chang, J; Hu, Z; Wei, L; Huang, Y; Han, Y; Liu, J; Han, D; Shen, H; Yang, S; Zheng, H; Ji, Q; Li, D; Tan, W; Wu, C; Lin, D

MLA Citation

Wei, Q, Yu, D, Liu, M, Wang, M, Zhao, M, Liu, M, Jia, W, Ma, H, Fang, J, Xu, W, Chen, K, Xu, Z, Wang, J, Tian, L, Yuan, H, Chang, J, Hu, Z, Wei, L, Huang, Y, Han, Y, Liu, J, Han, D, Shen, H, Yang, S, Zheng, H, Ji, Q, Li, D, Tan, W, Wu, C, and Lin, D. "Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population." Nature genetics 46.10 (October 2014): 1110-1114.

PMID

25194280

Source

epmc

Published In

Nature Genetics

Volume

46

Issue

10

Publish Date

2014

Start Page

1110

End Page

1114

DOI

10.1038/ng.3090

Functional polymorphisms of tumor necrosis factor-alpha (TNF-α) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF-α gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF-α polymorphisms and risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP). We used log-rank test and multivariable Cox models to evaluate the associations between TNF-α polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF-α -857 CC, TNF-α -863 CC and TNF-α -1031 TT genotypes had significantly worse disease-free survival (log-rank, p = 0.014, log-rank, p = .020, and log-rank, p = .002, respectively) and higher risk of disease recurrence than patients with the corresponding variant genotypes, respectively (hazard ratio [HR], 1.4, 95% CI, 1.1-1.9, HR, 1.4, 95% CI, 1.0-1.8 and HR, 1.6, 95% CI, 1.2-2.2, respectively). However, no significant association was detected for the TNF-α -308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms with risk of recurrence were more pronounced in smokers and patients treated with chemoradiation. Our findings support a significant role of the TNF-α -857, TNF-α -863 and TNF-α -1031 polymorphisms in recurrence of SCCNOP, especially in smokers and patients treated with chemoradiation. Future prospective studies with larger sample size are needed to confirm these findings.

Authors

Zhang, C; Sturgis, EM; Zheng, H; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Zhang, C, Sturgis, EM, Zheng, H, Zafereo, ME, Wei, Q, and Li, G. "TNF-α promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx." International journal of cancer 135.7 (October 2014): 1615-1624.

PMID

24550071

Source

epmc

Published In

International Journal of Cancer

Volume

135

Issue

7

Publish Date

2014

Start Page

1615

End Page

1624

DOI

10.1002/ijc.28793

Human papillomavirus (HPV)-positive oropharyngeal cancers represent a distinct clinical entity with more favorable prognosis than do HPV-negative oropharyngeal cancers. However, among patients with HPV-positive oropharyngeal carcinomas, those with a significant smoking history have a much worse prognosis. Recently, imaging characteristics of oropharyngeal cancers were identified as markers of poor prognosis. The purpose of this study was to determine whether nodal imaging characteristics differ between smokers and never/light smokers with HPV-positive oropharyngeal cancer.A review of 130 pretreatment computed tomographic examinations of HPV-positive oropharyngeal cancers in smokers (>10 pack-years) and never/light smokers (10 pack-years) matched for T stage and tumor subsite was performed, with the reviewing radiologist blinded to the HPV status, smoking history, and clinical stage. Additionally 24 pretreatment computed tomographic examinations of patients with HPV-negative oropharyngeal cancers were also reviewed in a blinded fashion. Imaging characteristics of metastatic nodal disease were compared using the testing (Fisher exact testing where appropriate) and McNemar testing for the matched-pair analysis.As expected, those with HPV-positive oropharyngeal cancer were more likely to be younger, male, non-Hispanic white, never/former smokers, and never drinkers than were those with HPV-negative oropharyngeal cancer. Furthermore, the HPV-positive oropharyngeal cancers were more likely to be in the tonsil, smaller T category, higher N category, poorly differentiated, than were the HPV-negative oropharyngeal cancers. However, among the HPV-positive oropharyngeal cancers, we could identify no obvious difference in the pretreatment imaging characteristics of paired smokers and never/light smokers.Among the patients with HPV-positive oropharyngeal cancer, no imaging characteristics were identified to correlate with the critical prognostic feature smoking status. Cystic and necrotic nodal metastases, as described previously, were more common among the patients with HPV-positive than those with HPV-negative oropharyngeal cancers. Although cystic nodal metastases were more common among the never/light smokers with HPV-positive oropharyngeal cancer than among smokers with HPV-positive oropharyngeal cancer, however, because these results did not reach statistical significance, we concluded that the imaging results cannot serve as a surrogate for an HPV-driven phenotype.

Authors

Cantrell, SC; Reid, HH; Li, G; Wei, Q; Sturgis, EM; Ginsberg, LE

MLA Citation

Cantrell, SC, Reid, HH, Li, G, Wei, Q, Sturgis, EM, and Ginsberg, LE. "Influence of smoking history on imaging characteristics among patients with human papillomavirus-positive oropharyngeal cancer: a blinded matched-pair analysis." Journal of computer assisted tomography 38.5 (September 2014): 667-673.

PMID

24943254

Source

epmc

Published In

Journal of Computer Assisted Tomography

Volume

38

Issue

5

Publish Date

2014

Start Page

667

End Page

673

DOI

10.1097/rct.0000000000000100

Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ≤1 risk genotypes, those with ≥2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ≥2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients.

Authors

Li, Y; Liu, Z; Liu, H; Wang, L-E; Onodera, H; Suzuki, A; Suzuki, K; Wadhwa, R; Elimova, E; Sudo, K; Shiozaki, H; Estrella, J; Lee, J-S; Song, S; Tan, D; Ajani, JA; Wei, Q

MLA Citation

Li, Y, Liu, Z, Liu, H, Wang, L-E, Onodera, H, Suzuki, A, Suzuki, K, Wadhwa, R, Elimova, E, Sudo, K, Shiozaki, H, Estrella, J, Lee, J-S, Song, S, Tan, D, Ajani, JA, and Wei, Q. "Potentially functional variants in the core nucleotide excision repair genes predict survival in Japanese gastric cancer patients." Carcinogenesis 35.9 (September 2014): 2031-2038.

PMID

24990617

Source

epmc

Published In

Carcinogenesis

Volume

35

Issue

9

Publish Date

2014

Start Page

2031

End Page

2038

DOI

10.1093/carcin/bgu142

Although genetic studies have reported a number of loci associated with melanoma risk, the complex genetic architecture of the disease is not yet fully understood. We sought to identify common genetic variants associated with melanoma risk in a genome-wide association study (GWAS) of 2298 cases and 6654 controls. Thirteen of 15 known loci were replicated with nominal significance. A total of 69 single-nucleotide polymorphisms (SNPs) were selected for in silico replication in two independent melanoma GWAS datasets (a total of 5149 cases and 12 795 controls). Seven novel loci were nominally significantly associated with melanoma risk. These seven SNPs were further genotyped in 234 melanoma cases and 238 controls. The SNP rs4698934 was nominally significantly associated with melanoma risk. The combined odds ratio per T allele = 1.18; 95% confidence interval (1.10-1.25); combined P = 7.70 × 10(-) (7). This SNP is located in the intron of the TET2 gene on chromosome 4q24. In addition, a novel somatic mutation of TET2 was identified by next-generation sequencing in 1 of 22 sporadic melanoma cases. TET2 encodes a member of TET family enzymes that oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). It is a putative epigenetic biomarker of melanoma as we previously reported, with observation of reduced TET2 transcriptional expression. This study is the first to implicate TET2 genetic variation and mutation in melanoma.

Authors

Song, F; Amos, CI; Lee, JE; Lian, CG; Fang, S; Liu, H; MacGregor, S; Iles, MM; Law, MH; Lindeman, NI; Montgomery, GW; Duffy, DL; Cust, AE; Jenkins, MA; Whiteman, DC; Kefford, RF; Giles, GG; Armstrong, BK; Aitken, JF; Hopper, JL; Brown, KM; Martin, NG; Mann, GJ; Bishop, DT; Bishop, JAN; GenoMEL consortium, ; Kraft, P; Qureshi, AA; Kanetsky, PA; Hayward, NK; Hunter, DJ; Wei, Q; Han, J

MLA Citation

Song, F, Amos, CI, Lee, JE, Lian, CG, Fang, S, Liu, H, MacGregor, S, Iles, MM, Law, MH, Lindeman, NI, Montgomery, GW, Duffy, DL, Cust, AE, Jenkins, MA, Whiteman, DC, Kefford, RF, Giles, GG, Armstrong, BK, Aitken, JF, Hopper, JL, Brown, KM, Martin, NG, Mann, GJ, Bishop, DT, Bishop, JAN, GenoMEL consortium, , Kraft, P, Qureshi, AA, Kanetsky, PA, Hayward, NK, Hunter, DJ, Wei, Q, and Han, J. "Identification of a melanoma susceptibility locus and somatic mutation in TET2." Carcinogenesis 35.9 (September 2014): 2097-2101.

PMID

24980573

Source

epmc

Published In

Carcinogenesis

Volume

35

Issue

9

Publish Date

2014

Start Page

2097

End Page

2101

DOI

10.1093/carcin/bgu140

LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy.We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders.Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32-6.72 and 1.01-4.94, P=0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24-4.28 and 1.11-3.62, and P=0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy.Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings.

Authors

Wen, J; Liu, H; Wang, Q; Liu, Z; Li, Y; Xiong, H; Xu, T; Li, P; Wang, L-E; Gomez, DR; Mohan, R; Komaki, R; Liao, Z; Wei, Q

MLA Citation

Wen, J, Liu, H, Wang, Q, Liu, Z, Li, Y, Xiong, H, Xu, T, Li, P, Wang, L-E, Gomez, DR, Mohan, R, Komaki, R, Liao, Z, and Wei, Q. "Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy." European journal of cancer (Oxford, England : 1990) 50.10 (July 2014): 1706-1716.

PMID

24780874

Source

epmc

Published In

European Journal of Cancer

Volume

50

Issue

10

Publish Date

2014

Start Page

1706

End Page

1716

DOI

10.1016/j.ejca.2014.03.008

Epistasis, or gene-gene interaction, results from joint effects of genes on a trait; thus, the same alleles of one gene may display different genetic effects in different genetic backgrounds. In this study, we generalized the coding technique of a natural and orthogonal interaction (NOIA) model for association studies along with gene-gene interactions for dichotomous traits and human complex diseases. The NOIA model which has non-correlated estimators for genetic effects is important for estimating influence from multiple loci. We conducted simulations and data analyses to evaluate the performance of the NOIA model. Both simulation and real data analyses revealed that the NOIA statistical model had higher power for detecting main genetic effects and usually had higher power for some interaction effects than the usual model. Although associated genes have been identified for predisposing people to melanoma risk: HERC2 at 15q13.1, MC1R at 16q24.3 and CDKN2A at 9p21.3, no gene-gene interaction study has been fully explored for melanoma. By applying the NOIA statistical model to a genome-wide melanoma dataset, we confirmed the previously identified significantly associated genes and found potential regions at chromosomes 5 and 4 that may interact with the HERC2 and MC1R genes, respectively. Our study not only generalized the orthogonal NOIA model but also provided useful insights for understanding the influence of interactions on melanoma risk.

Authors

Xiao, F; Ma, J; Cai, G; Fang, S; Lee, JE; Wei, Q; Amos, CI

MLA Citation

Xiao, F, Ma, J, Cai, G, Fang, S, Lee, JE, Wei, Q, and Amos, CI. "Natural and orthogonal model for estimating gene-gene interactions applied to cutaneous melanoma." Human genetics 133.5 (May 2014): 559-574.

PMID

24241239

Source

epmc

Published In

Human Genetics

Volume

133

Issue

5

Publish Date

2014

Start Page

559

End Page

574

DOI

10.1007/s00439-013-1392-2

The promoter variants of TNF-α, a major regulator of immune and inflammation responses, have been implicated in cancer development and prognosis. Thus, we investigated associations between four TNF-α promoter variants and risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated associations of four TNF-α polymorphisms with risk of recurrence in a cohort of 846 patients with SCCOP. Log-rank test and multivariable Cox models were used to evaluate associations. Compared with patients with variant genotypes of the TNF-α -308 and TNF-α -863 polymorphisms, patients with common homozygous genotypes had worse disease-free survival (log-rank p = 0.0002 and p < 0.0001, respectively) and increased risk of SCCOP recurrence (HR, 1.9, 95% CI, 1.3-2.8 and HR, 1.9, 95% CI, 1.3-2.7, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of the TNF-α -308 and -863 polymorphisms had worse disease-free survival (log-rank p = 0.005 and p = 0.007, respectively) and higher recurrence risk than patients with variant genotypes of these polymorphisms (HR, 5.1, 95% CI, 1.4-18.4 and HR, 3.7, 95% CI, 1.5-9.1, respectively), while no such significant associations were found for TNF-α -857 or -1031 polymorphisms. Our findings suggest that TNF-α -308 and -863 polymorphisms may modulate the risk of SCCOP recurrence in patients with HPV16-positive tumors. However, larger studies are needed to validate these results.

Authors

Zhang, C; Sturgis, EM; Zheng, H; Song, X; Wei, P; Jin, L; Chao, L; Wei, Q; Li, G

MLA Citation

Zhang, C, Sturgis, EM, Zheng, H, Song, X, Wei, P, Jin, L, Chao, L, Wei, Q, and Li, G. "Genetic variants in TNF-α promoter are predictors of recurrence in patients with squamous cell carcinoma of oropharynx after definitive radiotherapy." International journal of cancer 134.8 (April 2014): 1907-1915.

PMID

24122460

Source

epmc

Published In

International Journal of Cancer

Volume

134

Issue

8

Publish Date

2014

Start Page

1907

End Page

1915

DOI

10.1002/ijc.28512

Background RASSF3 suppresses tumour formation through uncertain mechanisms, but it is an important gene of p53-dependent apoptosis. RASSF3 depletion impairs DNA repair after DNA damage, leading to polyploidy. The authors hypothesised that potential functional single-nucleotide polymorphisms (SNPs) of RASSF3 are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). Methods The authors used a functional SNP approach to evaluate the associations between common (minor allele frequency ≥ 0.05), putative functional variants in RASSF3 and risk of SCCHN. Four selected such functional SNPs (rs6581580 T > G, rs7313765 G > A, rs12311754 G > C and rs1147098 T > C) in RASSF3 were identified and genotyped in 1087 patients and 1090 cancer-free controls in a non-Hispanic white population. Results The authors found that two SNPs were significantly associated with SCCHN risk. Carriers of the variant rs6581580G and rs7313765A alleles were at a reduced SCCHN risk, compared with the corresponding common homozygotes [adjusted odds ratio (OR) = 0.75 and 0.73 and 95% confidence interval (CI) = 0.62-0.91 and 0.60-0.88, respectively, for dominant models; and P trend = 0.012 and 0.041, respectively, for additive models], particularly for non-oropharyngeal tumours (adjusted OR = 0.68 and 0.60 and 95% CI = 0.53-0.86 and 0.47-0.77, respectively, for dominant models). In the genotype-phenotype correlation analysis of peripheral blood mononuclear cells from 102 cancer-free controls, the rs6581580 GG genotype was associated with significantly increased expression levels of RASSF3 mRNA (P = 0.038), compared with the TT genotype. Additional functional experiments further showed that variant G allele of rs6581580 had a significantly stronger binding affinity to the nuclear protein extracts than the T allele. Conclusion Taken together, these findings indicate that the RASSF3 promoter rs6581580 T > G SNP is potentially functional, modulating susceptibility to SCCHN among non-Hispanic whites. Larger replication studies are needed to confirm our findings. © 2013 Elsevier Ltd. All rights reserved.

Authors

Guo, H; Liu, H; Wei, J; Li, Y; Yu, H; Guan, X; Li-E, W; Li, G; Sturgis, EM; Wei, Q; Liu, Z

MLA Citation

Guo, H, Liu, H, Wei, J, Li, Y, Yu, H, Guan, X, Li-E, W, Li, G, Sturgis, EM, Wei, Q, and Liu, Z. "Functional single nucleotide polymorphisms of the RASSF3 gene and susceptibility to squamous cell carcinoma of the head and neck." European Journal of Cancer 50.3 (February 1, 2014): 582-592.

Source

scopus

Published In

European Journal of Cancer

Volume

50

Issue

3

Publish Date

2014

Start Page

582

End Page

592

DOI

10.1016/j.ejca.2013.11.009

The promoter of p53 induced gene 3 (PIG3) contains a variable number of tandem repeats (VNTRs) of pentanucleotides (TGYCC)n that is known as a p53 binding site. In this study, we investigated whether other potential molecules could bind to this PIG3 promoter (TGYCC)n motif. Ligand-chromatography combined with liquid chromatography-tandem mass spectrometry analyses indicated direct interactions of prohibitin and/or prohibiton with the (TGYCC)15 motif, which was confirmed by electrophoretic mobility shift assay and super-gel shift analysis with anti-prohibitin and anti-prohibiton antibodies. Using the chromatin immunopercipipation assay, we further demonstrated that prohibitin and prohibiton associated with the (TGYCC)15 motif in vivo regardless of the p53 status and apoptotic stress. We also found that prohibitin and prohibiton up-regulated PIG3 transcription independent of p53, although p53 obviously enhanced this process, and that the knock-down of prohibitin and prohibiton inhibited camptothecin-induced apoptosis. Taken together, our findings suggest that prohibitin and prohibiton contribute to PIG3-mediated apoptosis by binding to the PIG3 promoter (TGYCC)15 motif.

Authors

Guan, X; Liu, Z; Wang, L; Johnson, DG; Wei, Q

MLA Citation

Guan, X, Liu, Z, Wang, L, Johnson, DG, and Wei, Q. "Identification of prohibitin and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)(15) motif." Biochem Biophys Res Commun 443.4 (January 24, 2014): 1239-1244.

PMID

24388982

Source

pubmed

Published In

Biochemical and Biophysical Research Communications

Volume

443

Issue

4

Publish Date

2014

Start Page

1239

End Page

1244

DOI

10.1016/j.bbrc.2013.12.124

The promoter of p53 induced gene 3 (PIG3) contains a variable number of tandem repeats (VNTRs) of pentanucleotides (TGYCC)n that is known as a p53 binding site. In this study, we investigated whether other potential molecules could bind to this PIG3 promoter (TGYCC)n motif. Ligand-chromatography combined with liquid chromatography-tandem mass spectrometry analyses indicated direct interactions of prohibitin and/or prohibiton with the (TGYCC) 15 motif, which was confirmed by electrophoretic mobility shift assay and super-gel shift analysis with anti-prohibitin and anti-prohibiton antibodies. Using the chromatin immunopercipipation assay, we further demonstrated that prohibitin and prohibiton associated with the (TGYCC) 15 motif in vivo regardless of the p53 status and apoptotic stress. We also found that prohibitin and prohibiton up-regulated PIG3 transcription independent of p53, although p53 obviously enhanced this process, and that the knock-down of prohibitin and prohibiton inhibited camptothecin-induced apoptosis. Taken together, our findings suggest that prohibitin and prohibiton contribute to PIG3-mediated apoptosis by binding to the PIG3 promoter (TGYCC) 15 motif. © 2013 Elsevier Inc. All rights reserved.

Authors

Guan, X; Liu, Z; Wang, L; Johnson, DG; Wei, Q

MLA Citation

Guan, X, Liu, Z, Wang, L, Johnson, DG, and Wei, Q. "Identification of prohibitin and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)15 motif." Biochemical and Biophysical Research Communications 443.4 (January 24, 2014): 1239-1244.

Source

scopus

Published In

Biochemical and Biophysical Research Communications

Volume

443

Issue

4

Publish Date

2014

Start Page

1239

End Page

1244

DOI

10.1016/j.bbrc.2013.12.124

Authors

Li, Q; Gu, C; Zhu, Y; Wang, M; Yang, Y; Wang, J; Jin, L; Zhu, M-L; Shi, T-Y; He, J; Zhou, X; Ye, D-W; Wei, Q

MLA Citation

Li, Q, Gu, C, Zhu, Y, Wang, M, Yang, Y, Wang, J, Jin, L, Zhu, M-L, Shi, T-Y, He, J, Zhou, X, Ye, D-W, and Wei, Q. "Correction: Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population." Ed. X Miao. PLoS ONE 9.1 (January 6, 2014).

Source

crossref

Published In

PloS one

Volume

9

Issue

1

Publish Date

2014

DOI

10.1371/annotation/bc36c048-60e4-48a2-908d-6253e93df062

Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.

Authors

Chen, K; Ma, H; Li, L; Zang, R; Wang, C; Song, F; Shi, T; Yu, D; Yang, M; Xue, W; Dai, J; Li, S; Zheng, H; Wu, C; Zhang, Y; Wu, X; Li, D; Xue, F; Li, H; Jiang, Z; Liu, J; Liu, Y; Li, P; Tan, W; Han, J; Jie, J; Hao, Q; Hu, Z; Lin, D; Ma, D; Jia, W; Shen, H; Wei, Q

MLA Citation

Chen, K, Ma, H, Li, L, Zang, R, Wang, C, Song, F, Shi, T, Yu, D, Yang, M, Xue, W, Dai, J, Li, S, Zheng, H, Wu, C, Zhang, Y, Wu, X, Li, D, Xue, F, Li, H, Jiang, Z, Liu, J, Liu, Y, Li, P, Tan, W, Han, J, Jie, J, Hao, Q, Hu, Z, Lin, D, Ma, D, Jia, W, Shen, H, and Wei, Q. "Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women." Nature communications 5 (January 2014): 4682-.

PMID

25134534

Source

epmc

Published In

Nature Communications

Volume

5

Publish Date

2014

Start Page

4682

DOI

10.1038/ncomms5682

ERCC2 is indispensable for nucleotide excision repair pathway, and its functional polymorphisms may be associated with cancer risk. In a large case-control study of 1126 esophageal squamous cell carcinomas (ESCC) patients and 1131 controls, we genotyped two SNPs in ERCC2 (rs238406 G > T and rs13181 T > G) and assessed their associations with ESCC risk. We found a significantly elevated ESCC risk associated with the rs238406 T variant genotypes (adjusted OR = 1.30 and 1.24, 95% CI = 1.02-1.66 and 1.03-1.49 for TG and TG/TT, respectively, compared with GG), particularly in the subgroup of those smoked more than 16 pack-years. Multivariate logistic regression analysis suggested a possible multiplicative gene-environment interaction between rs238406 genotypes and smoking (Pinteraction = 0.026) on ESCC risk. Although no significant risk associations were observed for rs13181, further mini meta-analysis with our and 18 other published studies of 5,012 cases and 8,238 controls found evidence of an association between the rs13181 variant G allele and esophageal cancer risk (TG/GG vs. TT, OR = 1.17; 95% CI = 1.02-1.33). Interestingly, we consistently found a significant correlation between variant genotypes of these two SNPs and ERCC2 mRNA expression. These findings suggest that potentially functional SNPs in ERCC2 may contribute to ESCC risk.

Authors

Zhu, M-L; He, J; Wang, M; Sun, M-H; Jin, L; Wang, X; Yang, Y-J; Wang, J-C; Zheng, L; Xiang, J-Q; Wei, Q-Y

MLA Citation

Zhu, M-L, He, J, Wang, M, Sun, M-H, Jin, L, Wang, X, Yang, Y-J, Wang, J-C, Zheng, L, Xiang, J-Q, and Wei, Q-Y. "Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations." Scientific reports 4 (January 2014): 6281-.

PMID

25209371

Source

epmc

Published In

Scientific Reports

Volume

4

Publish Date

2014

Start Page

6281

DOI

10.1038/srep06281

The incidence of oropharyngeal and oral tongue cancers has increased over the last 20 years which parallels increased use of marijuana among individuals born after 1950.A pooled analysis was conducted comprising individual-level data from nine case-control studies from the United States and Latin America in the INHANCE consortium. Self-reported information on marijuana smoking, demographic, and behavioral factors was obtained from 1,921 oropharyngeal cases, 356 oral tongue cases, and 7,639 controls.Compared with never marijuana smokers, ever marijuana smokers had an elevated risk of oropharyngeal [adjusted OR (aOR), 1.24; 95% confidence interval (CI): 1.06-1.47] and a reduced risk of oral tongue cancer (aOR, 0.47; 95% CI, 0.29, 0.75). The risk of oropharyngeal cancer remained elevated among never tobacco and alcohol users. The risk of oral tongue cancer was reduced among never users of tobacco and alcohol. Sensitivity analysis adjusting for potential confounding by HPV exposure attenuated the association of marijuana use with oropharyngeal cancer (aOR, 0.99; 95% CI, 0.71-1.25), but had no effect on the oral tongue cancer association.These results suggest that the association of marijuana use with head and neck carcinoma may differ by tumor site.The associations of marijuana use with oropharyngeal and oral tongue cancer are consistent with both possible pro- and anticarcinogenic effects of cannabinoids. Additional work is needed to rule out various sources of bias, including residual confounding by HPV infection and misclassification of marijuana exposure.

Authors

Marks, MA; Chaturvedi, AK; Kelsey, K; Straif, K; Berthiller, J; Schwartz, SM; Smith, E; Wyss, A; Brennan, P; Olshan, AF; Wei, Q; Sturgis, EM; Zhang, Z-F; Morgenstern, H; Muscat, J; Lazarus, P; McClean, M; Chen, C; Vaughan, TL; Wunsch-Filho, V; Curado, MP; Koifman, S; Matos, E; Menezes, A; Daudt, AW; Fernandez, L; Posner, M; Boffetta, P; Lee, Y-CA; Hashibe, M; D'Souza, G

MLA Citation

Marks, MA, Chaturvedi, AK, Kelsey, K, Straif, K, Berthiller, J, Schwartz, SM, Smith, E, Wyss, A, Brennan, P, Olshan, AF, Wei, Q, Sturgis, EM, Zhang, Z-F, Morgenstern, H, Muscat, J, Lazarus, P, McClean, M, Chen, C, Vaughan, TL, Wunsch-Filho, V, Curado, MP, Koifman, S, Matos, E, Menezes, A, Daudt, AW, Fernandez, L, Posner, M, Boffetta, P, Lee, Y-CA, Hashibe, M, and D'Souza, G. "Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 23.1 (January 2014): 160-171.

PMID

24351902

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

23

Issue

1

Publish Date

2014

Start Page

160

End Page

171

DOI

10.1158/1055-9965.epi-13-0181

Since p14 (ARF) and human papillomavirus (HPV) 16 E6/E7 oncoproteins are important regulators participating in the p53/Rb pathways, genetic variations of p14 (ARF) may modify tumor HPV16 status and survival of HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) patients. We determined tumor HPV16 status and expression of p14/p53 and genotyped p14 (ARF) -rs3731217 and -rs3088440 polymorphisms in 552 incident SCCOP patients. We found that patients having variant genotypes for each p14 (ARF) polymorphism were approximately two or three times as likely to have HPV16-positive tumors compared with patients with corresponding common homozygous genotype, and such an association was particularly pronounced in patients with variant genotypes of both polymorphisms. After definitive chemoradiotherapy, patients having p14 (ARF) rs3731217 TG/GG variant genotypes had significantly better overall, disease-specific and disease-free survival than those having TT genotype, respectively. Multivariable analysis found that patients with p14 (ARF) -rs3731217 TT genotype had an ~7-, 11- and 3-fold increased risk for death overall, death due to SCCOP and recurrence than those with TG/GG variant genotypes, respectively. Furthermore, such significantly prognostic effect was also found when survival analysis was limited to HPV16-positive patients. Additionally, potentially functional relevance of the two variants was characterized to explore the genotype-phenotype correlation. Our findings indicate p14 (ARF) variants may predict tumor HPV16-positive SCCOP patients and survival.

Authors

Song, X; Sturgis, EM; Huang, Z; Li, X; Li, C; Wei, Q; Li, G

MLA Citation

Song, X, Sturgis, EM, Huang, Z, Li, X, Li, C, Wei, Q, and Li, G. "Potentially functional variants of p14ARF are associated with HPV-positive oropharyngeal cancer patients and survival after definitive chemoradiotherapy." Carcinogenesis 35.1 (January 2014): 62-68.

PMID

24104554

Source

epmc

Published In

Carcinogenesis

Volume

35

Issue

1

Publish Date

2014

Start Page

62

End Page

68

DOI

10.1093/carcin/bgt336

MicroRNAs are a new class of small non-protein-coding RNAs that sometimes function as tumor suppressors or oncogenes. Aberrant expression and structural alteration of microRNAs have been reported to be involved in tumorigenesis and cancer development. Recently, rs531564/pri-miR-124-1, rs4938723/pri-miR-34b/c, rs7372209/pri-miR-26a-1, rs895819/pre-miR-27a, and rs11134527/pri-miR-218 were reported to be associated with risks of various cancers. In order to evaluate the relationship of these SNPs and esophageal squamous cell carcinoma (ESCC) risk, we conducted a case-control study with 1109 ESCC patients and 1275 control subjects to examine the potential association of these pri/pre-miRNA polymorphisms with ESCC susceptibility. As a result, two SNPs were associated with a significant risk of ESCC. We found that the GG genotype of pri-miR-124-1 rs531564 was associated to a significantly decreased risk of ESCC comparing with the CC/CG genotypes (p = 0.005; OR = 0.61, 95% CI = 0.43-0.86). In addition, the CC genotype of pri-miR-34b/c rs4938723 was associated with a significant decreased risk of ESCC (CC VS.p = 0.007, OR = 0.82, 95% CI = 0.71-0.95) in Chinese population. The present study provides the first evidence that pri-miR-124-1 rs531564 and pri-miR-34 rs4938723 were associated with the risk of ESCC in Chinese population.

Authors

Zhang, J; Huang, X; Xiao, J; Yang, Y; Zhou, Y; Wang, X; Liu, Q; Yang, J; Wang, M; Qiu, L; Zheng, Y; Zhang, P; Li, J; Wang, Y; Wei, Q; Jin, L; Wang, J; Wang, M

MLA Citation

Zhang, J, Huang, X, Xiao, J, Yang, Y, Zhou, Y, Wang, X, Liu, Q, Yang, J, Wang, M, Qiu, L, Zheng, Y, Zhang, P, Li, J, Wang, Y, Wei, Q, Jin, L, Wang, J, and Wang, M. "Pri-miR-124 rs531564 and pri-miR-34b/c rs4938723 polymorphisms are associated with decreased risk of esophageal squamous cell carcinoma in Chinese populations." PloS one 9.6 (January 2014): e100055-.

PMID

24945256

Source

epmc

Published In

PloS one

Volume

9

Issue

6

Publish Date

2014

Start Page

e100055

DOI

10.1371/journal.pone.0100055

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. © 2014 UICC.

Authors

Conway, DI; Brenner, DR; Mcmahon, AD; Macpherson, LMD; Agudo, A; Ahrens, W; Bosetti, C; Brenner, H; Castellsague, X; Chen, C; Curado, MP; Curioni, OA; Maso, LD; Daudt, AW; Filho, JFDG; D'Souza, G; Edefonti, V; Fabianova, E; Fernandez, L; Franceschi, S; Gillison, M; Hayes, RB; Healy, CM; Herrero, R; Holcatova, I; Jayaprakash, V; Kelsey, K; Kjaerheim, K; Koifman, S; Vecchia, CL; Lagiou, P; Lazarus, P; Levi, F; Lissowska, J; Luce, D; Macfarlane, TV; Mates, D; Matos, E; Mcclean, M; Menezes, AM et al.

MLA Citation

Conway, DI, Brenner, DR, Mcmahon, AD, Macpherson, LMD, Agudo, A, Ahrens, W, Bosetti, C, Brenner, H, Castellsague, X, Chen, C, Curado, MP, Curioni, OA, Maso, LD, Daudt, AW, Filho, JFDG, D'Souza, G, Edefonti, V, Fabianova, E, Fernandez, L, Franceschi, S, Gillison, M, Hayes, RB, Healy, CM, Herrero, R, Holcatova, I, Jayaprakash, V, Kelsey, K, Kjaerheim, K, Koifman, S, Vecchia, CL, Lagiou, P, Lazarus, P, Levi, F, Lissowska, J, Luce, D, Macfarlane, TV, Mates, D, Matos, E, Mcclean, M, and Menezes, AM et al. "Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries." International Journal of Cancer (2014).

Source

scival

Published In

International Journal of Cancer

Publish Date

2014

DOI

10.1002/ijc.29063

Human papillomavirus (HPV)-positive oropharyngeal cancers represent a distinct clinical entity with more favorable prognosis than do HPV-negative oropharyngeal cancers. However, among patients with HPV-positive oropharyngeal carcinomas, those with a significant smoking history have a much worse prognosis. Recently, imaging characteristics of oropharyngeal cancers were identified as markers of poor prognosis. The purpose of this study was to determine whether nodal imaging characteristics differ between smokers and never/light smokers with HPV-positive oropharyngeal cancer. MATERIALS AND METHODS: A review of 130 pretreatment computed tomographic examinations of HPV-positive oropharyngeal cancers in smokers (>10 pack-years) and never/light smokers (10 pack-years) matched for T stage and tumor subsite was performed, with the reviewing radiologist blinded to the HPV status, smoking history, and clinical stage. Additionally 24 pretreatment computed tomographic examinations of patients with HPV-negative oropharyngeal cancers were also reviewed in a blinded fashion. Imaging characteristics of metastatic nodal disease were compared using the testing (Fisher exact testing where appropriate) and McNemar testing for the matched-pair analysis. RESULTS: As expected, those with HPV-positive oropharyngeal cancer were more likely to be younger, male, non-Hispanic white, never/former smokers, and never drinkers than were those with HPV-negative oropharyngeal cancer. Furthermore, the HPV-positive oropharyngeal cancers were more likely to be in the tonsil, smaller T category, higher N category, poorly differentiated, than were the HPV-negative oropharyngeal cancers. However, among the HPV-positive oropharyngeal cancers, we could identify no obvious difference in the pretreatment imaging characteristics of paired smokers and never/light smokers. CONCLUSIONS: Among the patients with HPV-positive oropharyngeal cancer, no imaging characteristics were identified to correlate with the critical prognostic feature smoking status. Cystic and necrotic nodal metastases, as described previously, were more common among the patients with HPV-positive than those with HPV-negative oropharyngeal cancers. Although cystic nodal metastases were more common among the never/light smokers with HPV-positive oropharyngeal cancer than among smokers with HPV-positive oropharyngeal cancer, however, because these results did not reach statistical significance, we concluded that the imaging results cannot serve as a surrogate for an HPV-driven phenotype.

Authors

Cantrell, SC; Reid, HH; Li, G; Wei, Q; Sturgis, EM; Ginsberg, LE

MLA Citation

Cantrell, SC, Reid, HH, Li, G, Wei, Q, Sturgis, EM, and Ginsberg, LE. "Influence of smoking history on imaging characteristics among patients with human papillomavirus-positive oropharyngeal cancer: A blinded matched-pair analysis." Journal of Computer Assisted Tomography (2014).

Source

scival

Published In

Journal of Computer Assisted Tomography

Publish Date

2014

DOI

10.1097/RCT.0000000000000100

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.

Authors

Stephens, SH; Hartz, SM; Hoft, NR; Saccone, NL; Corley, RC; Hewitt, JK; Hopfer, CJ; Breslau, N; Coon, H; Chen, X; Ducci, F; Dueker, N; Franceschini, N; Frank, J; Han, Y; Hansel, NN; Jiang, C; Korhonen, T; Lind, PA; Liu, J; Lyytikäinen, L-P; Michel, M; Shaffer, JR; Short, SE; Sun, J; Teumer, A; Thompson, JR; Vogelzangs, N; Vink, JM; Wenzlaff, A; Wheeler, W; Yang, B-Z; Aggen, SH; Balmforth, AJ; Baumeister, SE; Beaty, TH; Benjamin, DJ; Bergen, AW; Broms, U; Cesarini, D; Chatterjee, N; Chen, J et al.

MLA Citation

Stephens, SH, Hartz, SM, Hoft, NR, Saccone, NL, Corley, RC, Hewitt, JK, Hopfer, CJ, Breslau, N, Coon, H, Chen, X, Ducci, F, Dueker, N, Franceschini, N, Frank, J, Han, Y, Hansel, NN, Jiang, C, Korhonen, T, Lind, PA, Liu, J, Lyytikäinen, L-P, Michel, M, Shaffer, JR, Short, SE, Sun, J, Teumer, A, Thompson, JR, Vogelzangs, N, Vink, JM, Wenzlaff, A, Wheeler, W, Yang, B-Z, Aggen, SH, Balmforth, AJ, Baumeister, SE, Beaty, TH, Benjamin, DJ, Bergen, AW, Broms, U, Cesarini, D, Chatterjee, N, and Chen, J et al. "Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking." Genetic epidemiology 37.8 (December 2013): 846-859.

PMID

24186853

Source

epmc

Published In

Genetic Epidemiology

Volume

37

Issue

8

Publish Date

2013

Start Page

846

End Page

859

DOI

10.1002/gepi.21760

BACKGROUND: To assess the association between single nucleotide polymorphisms (SNPs) of base-excision repair genes and clinical outcomes, the roles of genetic variants of 3 selected genes-flap structure-specific endonuclease 1 (FEN1), 8-hydroxyguanine DNA glycosylase (hOGG1), and nei endonuclease VIII-like 1 (NEIL1)--were investigated in radiation-induced esophageal toxicity (RIET), radiation pneumonitis (RP), and overall survival (OS) after radio(chemo)therapy in patients with esophageal squamous cell carcinoma (ESCC). METHODS: NEIL1 reference SNP 4462560 (rs4462560) and rs7402844, hOGG1 rs1052133 and rs293795, and FEN1 rs4246215 and rs174538 were genotyped in 187 patients with ESCC who received definitive radiotherapy with or without chemotherapy. Kaplan-Meier cumulative probabilities and Cox proportional hazards regression models were used to assess the effect of the genotypes on the risk of RIET, RP, and OS. RESULTS: The authors observed that patients who had the NEIL1 rs4462560 GC/CC genotype had a statistically significantly lower risk of both grade ≥ 2 acute radiation-induced esophageal toxicity (RIET) (adjusted hazard ratio [HR], 0.421; 95% confidence interval [CI], 0.207-0.856; P = .017) and grade ≥ 2 acute radiation pneumonitis (RP) (adjusted HR, 0.392; 95% CI, 0.163-0.946; P = .037) compared with patients who had the GG genotype, but the genotype did not affect OS (adjusted HR, 0.778; 95% CI, 0.471-1.284; P = .326). There were no significant findings for other the SNPs under investigation. CONCLUSIONS: The NEIL1 rs4462560 SNP may serve as a predictor of acute RIET and RP risk but not of OS. Larger prospective studies are needed to validate these findings.

Authors

Chen, Y; Zhu, M; Zhang, Z; Jiang, G; Fu, X; Fan, M; Sun, M; Wei, Q; Zhao, K

MLA Citation

Chen, Y, Zhu, M, Zhang, Z, Jiang, G, Fu, X, Fan, M, Sun, M, Wei, Q, and Zhao, K. "A NEIL1 single nucleotide polymorphism (rs4462560) predicts the risk of radiation-induced toxicities in esophageal cancer patients treated with definitive radiotherapy." Cancer 119.23 (December 2013): 4205-4211.

PMID

24022861

Source

epmc

Published In

Cancer

Volume

119

Issue

23

Publish Date

2013

Start Page

4205

End Page

4211

DOI

10.1002/cncr.28338

Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.

Authors

He, J; Wang, M-Y; Qiu, L-X; Zhu, M-L; Shi, T-Y; Zhou, X-Y; Sun, M-H; Yang, Y-J; Wang, J-C; Jin, L; Wang, Y-N; Li, J; Yu, H-P; Wei, Q-Y

MLA Citation

He, J, Wang, M-Y, Qiu, L-X, Zhu, M-L, Shi, T-Y, Zhou, X-Y, Sun, M-H, Yang, Y-J, Wang, J-C, Jin, L, Wang, Y-N, Li, J, Yu, H-P, and Wei, Q-Y. "Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population." Molecular carcinogenesis 52 Suppl 1 (November 2013): E70-E79.

PMID

23423739

Source

epmc

Published In

Molecular Carcinogenesis

Volume

52 Suppl 1

Publish Date

2013

Start Page

E70

End Page

E79

DOI

10.1002/mc.22013

Gastric cancer imposes a considerable health burden around the globe despite its declining incidence. The disease is often diagnosed in advanced stages and is associated with a poor prognosis for patients. An in-depth understanding of the molecular underpinnings of gastric cancer has lagged behind many other cancers of similar incidence and morbidity, owing to our limited knowledge of germline susceptibility traits for risk and somatic drivers of progression (to identify novel therapeutic targets). A few germline (PLCE1) and somatic (ERBB2, ERBB3, PTEN, PI3K/AKT/mTOR, FGF, TP53, CDH1 and MET) alterations are emerging and some are being pursued clinically. Novel somatic gene targets (ARID1A, FAT4, MLL and KMT2C) have also been identified and are of interest. Variations in the therapeutic approaches dependent on geographical region are evident for localized gastric cancer-differences that are driven by preferences for the adjuvant strategies and the extent of surgery coupled with philosophical divides. However, greater uniformity in approach has been noted in the metastatic cancer setting, an incurable condition. Having realized only modest successes, momentum is building for carrying out more phase III comparative trials, with some using biomarker-based patient selection strategies. Overall, rapid progress in biotechnology is improving our molecular understanding and can help with new drug discovery. The future prospects are excellent for defining biomarker-based subsets of patients and application of specific therapeutics. However, many challenges remain to be tackled. Here, we review representative molecular and clinical dimensions of gastric cancer.

Authors

Wadhwa, R; Song, S; Lee, J-S; Yao, Y; Wei, Q; Ajani, JA

MLA Citation

Wadhwa, R, Song, S, Lee, J-S, Yao, Y, Wei, Q, and Ajani, JA. "Gastric cancer-molecular and clinical dimensions." Nature reviews. Clinical oncology 10.11 (November 2013): 643-655. (Review)

PMID

24061039

Source

epmc

Published In

Nature Reviews Clinical Oncology

Volume

10

Issue

11

Publish Date

2013

Start Page

643

End Page

655

DOI

10.1038/nrclinonc.2013.170

Background:Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial.Methods:We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue.Results:We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size.Conclusions:This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study. © 2013 Zhu et al.

Authors

Zhu, ML; Wang, MY; Shi, TY; Li, QX; Xi, P; Xia, KQ; Zheng, L; Wei, QY

MLA Citation

Zhu, ML, Wang, MY, Shi, TY, Li, QX, Xi, P, Xia, KQ, Zheng, L, and Wei, QY. "No Association between TGFB1 Polymorphisms and Late Radiotherapy Toxicity: A Meta-Analysis." PLoS ONE 8.10 (October 9, 2013).

Website

http://hdl.handle.net/10161/10673

PMID

24130819

Source

scopus

Published In

PloS one

Volume

8

Issue

10

Publish Date

2013

DOI

10.1371/journal.pone.0076964

XPC polymorphisms may alter DNA repair capacity, thus leading to genetic instability and carcinogenesis. Numerous studies have investigated the associations of XPC Lys939Gln (rs2228001) and Ala499Val (rs2228000) polymorphisms with cancer susceptibility; however, the findings are inconclusive. We searched literature from MEDLINE and EMBASE for eligible publications that assessed the associations between these two polymorphisms and cancer risk. We also assessed genotype-mRNA expression correlation data from HapMap for rs2228001 and rs2228000 in normal cell lines derived from 270 subjects with different ethnicities. The final analysis included 62 published studies of 25,708 cases and 30,432 controls for the Lys939Gln and 34 studies with 14,877 cases and 17,888 controls for the Ala499Val. Overall, Lys939Gln was significantly associated with an increased overall cancer risk (Gln/Gln vs. Lys/Lys: OR = 1.16, 95% CI = 1.07 - 1.25, p < 0.001; recessive model: OR = 1.14, 95% CI = 1.06 - 1.22, p < 0.001; dominant model: OR = 1.06, 95% CI = 1.01 - 1.11, p = 0.015 and Gln vs. Lys: OR = 1.07, 95% CI = 1.03 - 1.10, p < 0.001) and further stratifications showed an increased risk for bladder, lung and colorectal cancer, Asian populations and population-based studies. Likewise, Ala499Val was also significantly associated with an increased overall cancer risk (Val/Val vs. Ala/Ala: OR = 1.21, 95% CI = 1.07 - 1.36, p = 0.003 and recessive model: OR = 1.20, 95% CI = 1.08 - 1.34, p = 0.001) and further stratification showed an increased risk for breast and bladder cancer, particularly in Asian populations. Interestingly, significantly correlation between XPC genotypes and mRNA expression was found only for Asian populations as well. Despite some limitations, this meta-analysis established some solid statistical evidence for an association between XPC polymorphisms and cancer risk, which warrants further validation in single large studies.

Authors

He, J; Shi, T-Y; Zhu, M-L; Wang, M-Y; Li, Q-X; Wei, Q-Y

MLA Citation

He, J, Shi, T-Y, Zhu, M-L, Wang, M-Y, Li, Q-X, and Wei, Q-Y. "Associations of Lys939Gln and Ala499Val polymorphisms of the XPC gene with cancer susceptibility: a meta-analysis." International journal of cancer 133.8 (October 2013): 1765-1775.

PMID

23400628

Source

epmc

Published In

International Journal of Cancer

Volume

133

Issue

8

Publish Date

2013

Start Page

1765

End Page

1775

DOI

10.1002/ijc.28089

Sexual transmission of human papillomavirus (HPV), particularly HPV16, has been associated with an increasing incidence of oropharyngeal squamous cell carcinoma (OPC). Telomere shortening results in chromosomal instability, subsequently leading to cancer development. Given that HPV16 can affect telomerase activity and telomere length, we conjectured that telomere length in peripheral blood lymphocytes (PBL) might affect the risk of HPV16-associated OPC and tumor HPV16 status in patients. Telomere length in PBLs and HPV16 serologic status were measured in peripheral blood samples in 188 patients with OPC, 137 patients with oral cavity cancer (OCC) and 335 controls of non-Hispanic Whites. Tumor HPV status was determined in 349 OPC cases. ORs and 95% confidence intervals were calculated in univariate and multivariable logistic regression models. Overall, as compared with the long telomere length, short telomere length was significantly associated with a moderately increased risk of OPC but not with increased risk of OCC. When we stratified the data by HPV16 serologic status, using long telomere length and HPV16 seronegativity as the reference group, we found that the risk associated with HPV16 seropositivity was higher among patients with OPC with short telomere length. Notably, such risk was particularly pronounced in never smokers, never drinkers, and those more than 50 years of age. Furthermore, short telomere length was also associated significantly with tumor HPV-positive OPC. Together, our findings suggest that telomere length in PBLs may be associated with higher risk of HPV16-associated OPC and tumor HPV16 status, particularly in certain patient subgroups. Larger studies are needed to validate these findings.

Authors

Zhang, Y; Sturgis, EM; Dahlstrom, KR; Wen, J; Liu, H; Wei, Q; Li, G; Liu, Z

MLA Citation

Zhang, Y, Sturgis, EM, Dahlstrom, KR, Wen, J, Liu, H, Wei, Q, Li, G, and Liu, Z. "Telomere length in peripheral blood lymphocytes contributes to the development of HPV-associated oropharyngeal carcinoma." Cancer research 73.19 (October 2013): 5996-6003.

PMID

23928994

Source

epmc

Published In

Cancer Research

Volume

73

Issue

19

Publish Date

2013

Start Page

5996

End Page

6003

DOI

10.1158/0008-5472.can-13-0881

Human papillomavirus-positive oropharyngeal cancers typically have younger age of onset, limited tobacco exposure, and more favorable prognosis than HPV-negative oropharyngeal cancers. We assessed whether HPV-positive and HPV-negative oropharyngeal cancers have consistent differences in pretreatment imaging characteristics.A retrospective review of 136 pretreatment CT examinations of paired HPV-positive and HPV-negative oropharyngeal cancers matched for T stage, tumor subsite, and smoking status was performed with the reviewing radiologist blinded to HPV status and clinical stage. Demographic/clinical characteristics and imaging characteristics of primary lesions and metastatic nodal disease were compared by use of Fisher exact testing. The McNemar χ(2) test was used for the matched-pair analysis.By imaging, HPV-negative tumors were more likely to demonstrate invasion of adjacent muscle (26% versus 6%, P = .013). HPV-positive primary tumors were more likely to be enhancing and exophytic with well-defined borders, whereas HPV-negative primary tumors were more likely to be isoattenuated and demonstrate ill-defined borders, though these results were not statistically significant. HPV-positive tumors were more likely to demonstrate cystic nodal metastases than HPV-negative tumors (36% versus 9%, P = .002).In this matched and blinded analysis of the imaging differences between HPV-positive and HPV-negative oropharyngeal cancers, HPV-positive carcinomas often had primary lesions with well-defined borders and cystic nodal metastases, whereas HPV-negative primaries more often had poorly defined borders and invasion of adjacent muscle.

Authors

Cantrell, SC; Peck, BW; Li, G; Wei, Q; Sturgis, EM; Ginsberg, LE

MLA Citation

Cantrell, SC, Peck, BW, Li, G, Wei, Q, Sturgis, EM, and Ginsberg, LE. "Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis." AJNR. American journal of neuroradiology 34.10 (October 2013): 2005-2009.

PMID

23660291

Source

epmc

Published In

American Journal of Neuroradiology

Volume

34

Issue

10

Publish Date

2013

Start Page

2005

End Page

2009

DOI

10.3174/ajnr.a3524

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

Authors

Wyss, A; Hashibe, M; Chuang, S-C; Lee, Y-CA; Zhang, Z-F; Yu, G-P; Winn, DM; Wei, Q; Talamini, R; Szeszenia-Dabrowska, N; Sturgis, EM; Smith, E; Shangina, O; Schwartz, SM; Schantz, S; Rudnai, P; Purdue, MP; Eluf-Neto, J; Muscat, J; Morgenstern, H; Michaluart, P; Menezes, A; Matos, E; Mates, IN; Lissowska, J; Levi, F; Lazarus, P; La Vecchia, C; Koifman, S; Herrero, R; Hayes, RB; Franceschi, S; Wünsch-Filho, V; Fernandez, L; Fabianova, E; Daudt, AW; Dal Maso, L; Curado, MP; Chen, C et al.

MLA Citation

Wyss, A, Hashibe, M, Chuang, S-C, Lee, Y-CA, Zhang, Z-F, Yu, G-P, Winn, DM, Wei, Q, Talamini, R, Szeszenia-Dabrowska, N, Sturgis, EM, Smith, E, Shangina, O, Schwartz, SM, Schantz, S, Rudnai, P, Purdue, MP, Eluf-Neto, J, Muscat, J, Morgenstern, H, Michaluart, P, Menezes, A, Matos, E, Mates, IN, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Hayes, RB, Franceschi, S, Wünsch-Filho, V, Fernandez, L, Fabianova, E, Daudt, AW, Dal Maso, L, Curado, MP, and Chen, C et al. "Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium." American journal of epidemiology 178.5 (September 2013): 679-690.

PMID

23817919

Source

epmc

Published In

American Journal of Epidemiology

Volume

178

Issue

5

Publish Date

2013

Start Page

679

End Page

690

DOI

10.1093/aje/kwt029

Genetically determined capacity for NER may modulate both cancer risk and prognosis. Thus, we evaluated associations of seven selected variants in the NER core genes with recurrence risk in 658 squamous cell carcinoma of the oropharynx (SCCOP) patients treated principally by radiation. The seven polymorphisms in the core NER genes (XPC-rs2228000, XPC-rs2228001, XPD-rs1799793, XPD-rs13181, XPG-rs17655, ERCC1-rs3212986 and XPA-rs1800975) were genotyped using PCR-RFLP method and log-rank test and multivariable Cox models were used to evaluate the associations in both dominant and recessive genetic models. In a dominant model, we found that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 were significantly associated with disease-free survival (log-rank, p = 0.014; p = 0.00008; p = 0.0007, respectively), and these polymorphisms were significantly associated with recurrence risk of SCCOP (hazard ratio (HR) = 1.6, 95% confidence interval (CI) 1.1-2.3 for XPC-rs2228000; HR = 0.4, 95% 0.3-0.6 for XPD-rs1799793 and HR = 0.5, 95% CI 0.4-0.8 for XPG-rs17655) after multivariable adjustment. Moreover, the borderline significant or significant associations were also found for these three polymorphisms in HPV16/18-positive SCCOP patients (HR = 1.6, 95% CI 1.0-4.1 for XPC-rs2228000; HR = 0.2, 95% CI 0.1-0.5 for XPD-rs1799793 and HR = 0.1, 95% CI 0.0-0.9 for XPG-rs17655). However, similarly significant associations were not found for these polymorphisms in a recessive model. These findings suggest that polymorphisms of XPC-rs2228000, XPD-rs1799793 and XPG-rs17655 in the NER core genes may contribute to recurrence risk of SCCOP, particularly HPV-positive SCCOP, in a dominant but not in a recessive model. However, validation of these results is warranted.

Authors

Song, X; Sturgis, EM; Jin, L; Wang, Z; Wei, Q; Li, G

MLA Citation

Song, X, Sturgis, EM, Jin, L, Wang, Z, Wei, Q, and Li, G. "Variants in nucleotide excision repair core genes and susceptibility to recurrence of squamous cell carcinoma of the oropharynx." International journal of cancer 133.3 (August 2013): 695-704.

PMID

23335232

Source

epmc

Published In

International Journal of Cancer

Volume

133

Issue

3

Publish Date

2013

Start Page

695

End Page

704

DOI

10.1002/ijc.28051

Tumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).In this study we genotyped four common single nucleotide polymorphisms (SNPs) in the TNF-α promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).We found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.Taken together, these results suggest that TNF-α SNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.

Authors

Jin, L; Sturgis, EM; Zhang, Y; Huang, Z; Song, X; Li, C; Wei, Q; Li, G

MLA Citation

Jin, L, Sturgis, EM, Zhang, Y, Huang, Z, Song, X, Li, C, Wei, Q, and Li, G. "Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma." Molecular cancer 12 (July 19, 2013): 80-.

PMID

23870134

Source

epmc

Published In

Molecular Cancer

Volume

12

Publish Date

2013

Start Page

80

DOI

10.1186/1476-4598-12-80

A recent review of the Surveillance, Epidemiology, and End Results registry suggested that patients with index squamous cell carcinoma (SCC) of the oropharynx (SCCOP) are less likely to develop second primary malignancies (SPM) than patients with index SCC of nonoropharyngeal sites (oral cavity, larynx, hypopharynx). The objectives of this study were to determine the impact of index primary tumor site on SPM risk and to explore factors that potentially affect this risk within a large, prospectively accrued cohort of patients with index SCC of the head and neck (SCCHN).A cohort of 2230 patients with incident SCCHN was reviewed for development of SPM. Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards models were used to detect the impact of various factors, including index tumor site, on SPM risk.The SPM rate was lower for patients with index SCCOP than for patients with index nonoropharyngeal cancer (P < .001). Among patients with SCCOP, former smokers had a 50% greater risk of SPM, and current smokers had a 100% greater risk of SPM than never-smokers (Ptrend  = .008). Also among patients with SCCOP, those with the classic SCCHN phenotype had an SPM risk similar to that of patients with index nonoropharyngeal cancers; those with a typical human papillomavirus phenotype had a very low SPM risk. SPM most commonly occurred at nontobacco-related sites in patients with index SCCOP and at tobacco-related sites in patients with index nonoropharyngeal cancers.In patients with SCCHN, index cancer site and smoking status affect the risk and distribution of SPM.

Authors

Gan, SJ; Dahlstrom, KR; Peck, BW; Caywood, W; Li, G; Wei, Q; Zafereo, ME; Sturgis, EM

MLA Citation

Gan, SJ, Dahlstrom, KR, Peck, BW, Caywood, W, Li, G, Wei, Q, Zafereo, ME, and Sturgis, EM. "Incidence and pattern of second primary malignancies in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers." Cancer 119.14 (July 2013): 2593-2601.

PMID

23605777

Source

epmc

Published In

Cancer

Volume

119

Issue

14

Publish Date

2013

Start Page

2593

End Page

2601

DOI

10.1002/cncr.28107

Recently, several studies have investigated the association between a newly reported rare functional single nucleotide polymorphism (SNP) in TP53 (rs78378222) and cancer risk, but generated inconsistent findings. The present study further investigated this association with risk of melanoma, squamous cell carcinoma of head and neck (SCCHN) and lung cancer. Using volunteers of non-Hispanic Whites recruited for three large case-control studies, we genotyped the TP53 rs78378222 SNP in 1329 patients with melanoma, 1096 with SCCHN, 1013 with lung cancer and 3000 cancer-free controls. Overall, we did not observe any variant homozygotes in this study population, nor significant associations between the TP53 rs78378222AC genotype or C allele and risk for melanoma (P = 0.680 and 0.682 respectively) and lung cancer (P = 0.379 and 0.382 respectively), but a protection against SCCHN (P = 0.008 and 0.008 respectively), compared with the AA genotype or A allele. An additional meta-analysis including 19,423 cancer patients and 54,050 controls did not support such a risk association either. Our studies did not provide statistical evidence of an association between this rare TP53 variant and increased risk of melanoma, nor of lung cancer, but a possible protection against SCCHN.

Authors

Guan, X; Wang, L-E; Liu, Z; Sturgis, EM; Wei, Q

MLA Citation

Guan, X, Wang, L-E, Liu, Z, Sturgis, EM, and Wei, Q. "Association between a rare novel TP53 variant (rs78378222) and melanoma, squamous cell carcinoma of head and neck and lung cancer susceptibility in non-Hispanic Whites." Journal of cellular and molecular medicine 17.7 (July 2013): 873-878.

PMID

23742673

Source

epmc

Published In

Journal of Cellular and Molecular Medicine

Volume

17

Issue

7

Publish Date

2013

Start Page

873

End Page

878

DOI

10.1111/jcmm.12076

Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles = 0.12, P value = 4 × 10(-5)). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R (2) quality metric >0.8 using the 1,000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity.

Authors

Li, X; Liang, L; Zhang, M; Song, F; Nan, H; Wang, L-E; Wei, Q; Lee, JE; Amos, CI; Qureshi, AA; Han, J

MLA Citation

Li, X, Liang, L, Zhang, M, Song, F, Nan, H, Wang, L-E, Wei, Q, Lee, JE, Amos, CI, Qureshi, AA, and Han, J. "Obesity-related genetic variants, human pigmentation, and risk of melanoma." Human genetics 132.7 (July 2013): 793-801.

PMID

23539184

Source

epmc

Published In

Human Genetics

Volume

132

Issue

7

Publish Date

2013

Start Page

793

End Page

801

DOI

10.1007/s00439-013-1293-4

Aiming to identify novel genetic loci for pigmentation and skin cancer, we conducted a series of genome-wide association studies on hair color, eye color, number of sunburns, tanning ability and number of non-melanoma skin cancers (NMSCs) among 10 183 European Americans in the discovery stage and 4504 European Americans in the replication stage (for eye color, 3871 males in the discovery stage and 2496 males in the replication stage). We targeted novel chromosome regions besides the known ones for replication. As a result, we identified a new region downstream of the EDNRB gene on 13q22 associated with hair color and the strongest association was the single-nucleotide polymorphism (SNP) rs975739 (P = 2.4 × 10(-14); P = 5.4 × 10(-9) in the discovery set and P = 1.2 × 10(-6) in the replication set). Using blue, intermediate (including green) and brown eye colors as co-dominant outcomes, we identified the SNP rs3002288 in VASH2 on 1q32.3 associated with brown eye (P = 7.0 × 10(-8); P = 5.3 × 10(-5) in the discovery set and P = 0.02 in the replication set). Additionally, we identified a significant interaction between the SNPs rs7173419 and rs12913832 in the OCA2 gene region on brown eye color (P-value for interaction = 3.8 × 10(-3)). As for the number of NMSCs, we identified two independent SNPs on chr6 and one SNP on chromosome 14: rs12203592 in IRF4 (P = 7.2 × 10(-14); P = 1.8 × 10(-8) in the discovery set and P = 6.7 × 10(-7) in the replication set), rs12202284 between IRF4 and EXOC2 (P = 5.0 × 10(-8); P = 6.6 × 10(-7) in the discovery set and P = 3.0 × 10(-3) in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10(-8); P = 5.3 × 10(-7) in the discovery set and P = 0.01 in the replication set).

Authors

Zhang, M; Song, F; Liang, L; Nan, H; Zhang, J; Liu, H; Wang, L-E; Wei, Q; Lee, JE; Amos, CI; Kraft, P; Qureshi, AA; Han, J

MLA Citation

Zhang, M, Song, F, Liang, L, Nan, H, Zhang, J, Liu, H, Wang, L-E, Wei, Q, Lee, JE, Amos, CI, Kraft, P, Qureshi, AA, and Han, J. "Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans." Human molecular genetics 22.14 (July 2013): 2948-2959.

PMID

23548203

Source

epmc

Published In

Human Molecular Genetics

Volume

22

Issue

14

Publish Date

2013

Start Page

2948

End Page

2959

DOI

10.1093/hmg/ddt142

Because of their important roles in mediating the stabilization and expression of p53, we hypothesized that high-risk genotypes of polymorphisms in p53-related genes, including p53, p73, p14(ARF), MDM2 and MDM4, may be associated with an increased risk of second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). We analyzed data from a cohort of 1283 patients with index SCCHN who were recruited between 1995 and 2007 at MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for nine polymorphisms of p53-related genes. A log-rank test and Cox models were used to compare SPM-free survival and risk. Our results demonstrated that each p53-related polymorphism had a moderate effect on increased SPM risk, but when we combined risk genotypes of these nine polymorphisms together, we found that SPM-free survival was significantly shorter among risk groups with a greater number of combined risk genotypes. SPM risk increased with increasing number of risk genotypes (P < 0.0001 for trend). Compared with the low-risk group (0-3 combined risk genotypes), both the medium-risk (4-5 combined risk genotypes) and high-risk (6-9 combined risk genotypes) groups had significantly increased SPM risk [hazard ratio (HR): 1.6; 95% confidence interval (CI): 1.0-2.6 and HR: 3.0; 95% CI: 1.8-5.0, respectively]. Moreover, such significant associations were even higher in several subgroups. Our findings suggest that combined risk genotypes of p53-related genes may jointly modify SPM risk, especially in patients who are smokers and those with index non-oropharyngeal cancers. However, larger studies are needed to validate our findings.

Authors

Jin, L; Sturgis, EM; Zhang, Y; Huang, Z; Wei, P; Guo, W; Wang, Z; Wei, Q; Song, X; Li, G

MLA Citation

Jin, L, Sturgis, EM, Zhang, Y, Huang, Z, Wei, P, Guo, W, Wang, Z, Wei, Q, Song, X, and Li, G. "Genetic variants in p53-related genes confer susceptibility to second primary malignancy in patients with index squamous cell carcinoma of head and neck." Carcinogenesis 34.7 (July 2013): 1551-1557.

PMID

23508638

Source

epmc

Published In

Carcinogenesis

Volume

34

Issue

7

Publish Date

2013

Start Page

1551

End Page

1557

DOI

10.1093/carcin/bgt096

Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings.

Authors

Li, C; Yin, M; Wang, L-E; Amos, CI; Zhu, D; Lee, JE; Gershenwald, JE; Grimm, EA; Wei, Q

MLA Citation

Li, C, Yin, M, Wang, L-E, Amos, CI, Zhu, D, Lee, JE, Gershenwald, JE, Grimm, EA, and Wei, Q. "Polymorphisms of nucleotide excision repair genes predict melanoma survival." The Journal of investigative dermatology 133.7 (July 2013): 1813-1821.

PMID

23407396

Source

epmc

Published In

Journal of Investigative Dermatology

Volume

133

Issue

7

Publish Date

2013

Start Page

1813

End Page

1821

DOI

10.1038/jid.2012.498

INTRODUCTION: Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that functions as a key regulator of gene transcription, protein translation, and autophagy. No studies have assessed associations between functional single nucleotide polymorphisms (SNPs) in mTORC1 genes and risk of esophageal squamous cell carcinoma (ESCC). METHODS: : In a case-control study of 1126 ESCC patients and 1131 cancer-free controls, we genotyped eight SNPs in mTORC1 (mTOR rs1883965 G>A and rs2536 T>C, mLST8 rs3160 C>T and rs26865 G>A, RPTOR rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A) and assessed their associations with risk of ESCC. RESULTS: In the single-locus analyses, we found a significantly altered risk of ESCC associated with mTOR rs1883965 A variant genotypes (adjusted OR = 1.27 and 1.26; 95% confidence interval = 1.01-1.60 and 1.01-1.58 for GA and GA/AA, respectively, compared with GG) but not with other SNPs. In the combined analysis of the eight SNPs, we found individuals with two or more unfavorable genotypes exhibited an increased risk for ESCC (adjusted OR = 1.35; 95% confidence interval = 1.20-1.62), compared with those with less than two unfavorable genotypes. Such a cumulative effect was dose-dependent (ptrend = 0.004). In the multiple dimension reduction analysis, mTOR rs1883965 was consistently suggested as the strongest individual factor for ESCC risk, and the model including all SNPs yielded the lowest prediction error of 17.66% for model validation. CONCLUSIONS: These findings suggest that functional SNPs of mTORC1 genes may individually or collectively contribute to ESCC risk. Further validation of these findings is warranted.

Authors

Zhu, M-L; Yu, H; Shi, T-Y; He, J; Wang, M-Y; Li, Q-X; Sun, M-H; Jin, L; Yang, Y-J; Wang, J-C; Xiang, J-Q; Wei, Q-Y

MLA Citation

Zhu, M-L, Yu, H, Shi, T-Y, He, J, Wang, M-Y, Li, Q-X, Sun, M-H, Jin, L, Yang, Y-J, Wang, J-C, Xiang, J-Q, and Wei, Q-Y. "Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 8.6 (June 2013): 788-795.

PMID

23524405

Source

epmc

Published In

Journal of Thoracic Oncology

Volume

8

Issue

6

Publish Date

2013

Start Page

788

End Page

795

DOI

10.1097/jto.0b013e31828916c6

DNA Polymerase ζ (Polζ), an error-prone DNA polymerase involved in translesion DNA synthesis, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of several cancers. To evaluate the association of Polζ with chemoradiation resistance and prognosis in cervical cancer, we enrolled 123 patients with squamous cell carcinoma of cervical cancer, who had adjuvant concurrent chemoradiation therapy after radical surgery treated at Fudan University Shanghai Cancer Center between 2008 and 2009, and tested their in vitro tumor inhibition rates using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide method and Polζ protein expression in paraffin-embedded tissues using immunohistochemistry. We found that the Polζ-positive expression was detected in 22 % of the cases. The median in vitro inhibition rate of tumor cell growth by cisplatin, carboplatin, nedaplatin, and oxaliplatin was 80, 37, 78, and 51 %, respectively. Among the tumor-related variables, FIGO stage, tumor grade, and Polζ protein expression (adjusted HR 6.7, 4.2 and 6.7; 95 % CI 1.7-26.3, 1.0-17.3 and 1.8-25.4; P = 0.007, 0.046 and 0.005, respectively) were found to be significant predictors for recurrence. Kaplan-Meier survival estimates showed that the patients with more advanced stage (IIB) or Polζ-positive expression had a significantly shorter progression-free survival. Polζ-positive expression was significantly associated with depth of cervical stromal invasion (P = 0.012). However, the association between Polζ expression and in vitro tumor inhibition rates was not significant. Taken together, Polζ expression can be used as the predictor for poor prognosis, which might be caused by the potential chemoradiation resistance of the cervical cancer patients. The mechanism deserves further exploration.

Authors

Shi, T-Y; Yang, L; Yang, G; Tu, X-Y; Wu, X; Cheng, X; Wei, Q

MLA Citation

Shi, T-Y, Yang, L, Yang, G, Tu, X-Y, Wu, X, Cheng, X, and Wei, Q. "DNA polymerase ζ as a potential biomarker of chemoradiation resistance and poor prognosis for cervical cancer." Medical oncology (Northwood, London, England) 30.2 (June 2013): 500-.

PMID

23456618

Source

epmc

Published In

Medical Oncology

Volume

30

Issue

2

Publish Date

2013

Start Page

500

DOI

10.1007/s12032-013-0500-4

Among patients with index oropharyngeal cancer, second primary malignancies (SPMs) may be less common in cases of human papillomavirus (HPV)-associated tumors than HPV-negative tumors. Further modification of these SPM risks by smoking has not been reported.SPM outcomes of 356 patients with incident oropharyngeal cancer were analyzed using Cox proportional hazards and Kaplan-Meier models. SPM risk and SPM-free survival were compared in HPV-seronegative patients, HPV-seropositive never smokers, and HPV-seropositive ever smokers.HPV-seropositive patients had a lower 5-year SPM rate than HPV-seronegative patients (5.6% vs 14.6%; p = .051). Compared to HPV-seronegative patients, HPV-seropositive never smokers had a 73% reduced SPM risk, and HPV-seropositive ever smokers had a 27% reduced SPM risk (trend p = .028). Although HPV-seronegative patients had SPMs in traditional locations, 70% of SPMs among HPV-seropositive patients were outside typical tobacco-related sites.HPV serologic status and smoking may stratify patients with index oropharyngeal cancers in terms of risk and location of SPMs.

Authors

Peck, BW; Dahlstrom, KR; Gan, SJ; Caywood, W; Li, G; Wei, Q; Zafereo, ME; Sturgis, EM

MLA Citation

Peck, BW, Dahlstrom, KR, Gan, SJ, Caywood, W, Li, G, Wei, Q, Zafereo, ME, and Sturgis, EM. "Low risk of second primary malignancies among never smokers with human papillomavirus-associated index oropharyngeal cancers." Head & neck 35.6 (June 2013): 794-799.

PMID

22711172

Source

epmc

Published In

Head & Neck: Journal for the Sciences & Specialties of the Head and Neck

Volume

35

Issue

6

Publish Date

2013

Start Page

794

End Page

799

DOI

10.1002/hed.23033

Interleukin-10 (IL-10) plays an important role in a host's defense against human papillomavirus (HPV) infection. IL-10 promoter variants may affect its expression level or functional efficiency and, subsequently, susceptibility to and survival of HPV16-associated squamous cell carcinoma of oropharynx (SCCOP). We determined tumor HPV16 DNA and genotyped three IL-10 promoter polymorphisms in 309 incident patients with SCCOP. Compared with the patients with corresponding common homozygous genotypes, patients carrying variant genotypes of IL-10 rs1800871 and rs1800872 were ~2.5 times more likely to have HPV16(+) tumors among patients with SCCOP. Among HPV16(+) patients with SCCOP only, compared to those with the corresponding variant genotypes, the patients with IL-10 rs1800871 and rs1800872 CC genotypes had significantly better survival and ~70-80% reduced risk of death/recurrence after multivariable adjustment. Additionally, functional relevance of these variants was characterized to explore the genotype-phenotype correlation. Our findings indicate that IL-10 genetic variants may be associated with tumor HPV16(+) SCCOP and predict survival of HPV16(+) patients with SCCOP. Larger studies are needed to validate our findings.

Authors

Jin, L; Sturgis, EM; Cao, X; Song, X; Salahuddin, T; Wei, Q; Li, G

MLA Citation

Jin, L, Sturgis, EM, Cao, X, Song, X, Salahuddin, T, Wei, Q, and Li, G. "Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27.6 (June 2013): 2496-2503.

PMID

23430974

Source

epmc

Published In

The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Volume

27

Issue

6

Publish Date

2013

Start Page

2496

End Page

2503

DOI

10.1096/fj.12-226803

MLA Citation

"Molecular epidemiology of DNA repair gene polymorphisms and head and neck cancer." Journal of Biomedical Research (May 30, 2013).

Source

crossref

Published In

Journal of Biomedical Research

Publish Date

2013

DOI

10.7555/JBR.27.20130034

Angiogenesis and lymphangiogenesis are important in the progression of melanoma. We investigated associations between genetic variants in these pathways with sentinel lymph node (SLN) metastasis and mortality in 2 independent series of patients with melanoma.Participants at Moffitt Cancer Center were 552 patients, all Caucasian, with primary cutaneous melanoma referred for SLN biopsy. A total of 177 patients had SLN metastasis, among whom 60 died from melanoma. Associations between 238 single-nucleotide polymorphisms (SNP) in 26 genes and SLN metastasis were estimated as ORs and 95% confidence intervals (CI) using logistic regression. Competing risk regression was used to estimate HRs and 95% CI for each SNP and melanoma-specific mortality. We attempted to replicate significant findings using data from a genome-wide association study comprising 1,115 patients with melanoma who were referred for SLN biopsy from MD Anderson Cancer Center (MDACC), among whom 189 patients had SLN metastasis and 92 patients died from melanoma.In the Moffitt dataset, we observed significant associations in 18 SNPs with SLN metastasis and 17 SNPs with mortality. Multiple SNPs in COL18A1, EGF receptor (EGFR), FLT1, interleukin (IL)-10, platelet-derived growth factor D (PDGFD), PIK3CA, and toll-like receptor (TLR)-3 were associated with the risk of SLN metastasis and/or patient mortality. The MDACC data set replicated an association between mortality and rs2220377 in PDGFD. Furthermore, in a meta-analysis, 3 additional SNPs were significantly associated with SLN metastasis (EGFR rs723526 and TLR3 rs3775292) and melanoma-specific death (TLR3 rs7668666).These findings suggest that genetic variation in angiogenesis and lymphangiogenesis contributes to regional nodal metastasis and progression of melanoma.Additional research attempting to replicate these results is warranted.

Authors

Park, JY; Amankwah, EK; Anic, GM; Lin, H-Y; Walls, B; Park, H; Krebs, K; Madden, M; Maddox, K; Marzban, S; Fang, S; Chen, W; Lee, JE; Wei, Q; Amos, CI; Messina, JL; Sondak, VK; Sellers, TA; Egan, KM

MLA Citation

Park, JY, Amankwah, EK, Anic, GM, Lin, H-Y, Walls, B, Park, H, Krebs, K, Madden, M, Maddox, K, Marzban, S, Fang, S, Chen, W, Lee, JE, Wei, Q, Amos, CI, Messina, JL, Sondak, VK, Sellers, TA, and Egan, KM. "Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 22.5 (May 2013): 827-834.

PMID

23462921

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

22

Issue

5

Publish Date

2013

Start Page

827

End Page

834

DOI

10.1158/1055-9965.epi-12-1129

To mine possibly hidden causal single-nucleotide polymorphisms (SNPs) of melanoma, we investigated the association of SNPs in 76 M/G1 transition genes with melanoma risk using our published genome-wide association study (GWAS) data set with 1804 melanoma cases and 1026 cancer-free controls. We found multiple SNPs with P < 0.01 and performed validation studies for 18 putative functional SNPs in PSMB9 in two other GWAS data sets. Two SNPs (rs1351383 and rs2127675) were associated with melanoma risk in the GenoMEL data set (P = 0.013 and 0.004, respectively), but failed in validation using the Australian data set. Genotype-phenotype analysis revealed these two SNPs were significantly correlated with mRNA expression level of PSMB9. Further experiments revealed that SNP rs2071480, which is in high LD with rs1351383 and rs2127675, may have a weak effect on the promoter activity of PSMB9. Taken together, our data suggested that functional variants in PSMB9 may contribute to melanoma susceptibility.

Authors

Qian, J; Liu, H; Wei, S; Liu, Z; Li, Y; Wang, L-E; Chen, WV; Amos, CI; Lee, JE; GenoMEL investigators, ; Iles, MM; Law, MH; Q-MEGA AMFS investigators, ; Cust, AE; Barrett, JH; Montgomery, GW; Taylor, J; Bishop, JAN; Macgregor, S; Bishop, DT; Mann, GJ; Hayward, NK; Wei, Q

MLA Citation

Qian, J, Liu, H, Wei, S, Liu, Z, Li, Y, Wang, L-E, Chen, WV, Amos, CI, Lee, JE, GenoMEL investigators, , Iles, MM, Law, MH, Q-MEGA AMFS investigators, , Cust, AE, Barrett, JH, Montgomery, GW, Taylor, J, Bishop, JAN, Macgregor, S, Bishop, DT, Mann, GJ, Hayward, NK, and Wei, Q. "Association between putative functional variants in the PSMB9 gene and risk of melanoma--re-analysis of published melanoma genome-wide association studies." Pigment cell & melanoma research 26.3 (May 2013): 392-401.

PMID

23360169

Source

epmc

Published In

Pigment Cell and Melanoma Research

Volume

26

Issue

3

Publish Date

2013

Start Page

392

End Page

401

DOI

10.1111/pcmr.12069

Authors

Guan, X; Niu, J; Liu, Z; Wang, L-E; Amos, CI; Lee, JE; Gershenwald, JE; Grimm, EA; Wei, Q

MLA Citation

Guan, X, Niu, J, Liu, Z, Wang, L-E, Amos, CI, Lee, JE, Gershenwald, JE, Grimm, EA, and Wei, Q. "Variants in melanocortin 1 receptor gene contribute to risk of melanoma--a direct sequencing analysis in a Texas population." Pigment cell & melanoma research 26.3 (May 2013): 422-425. (Letter)

PMID

23360207

Source

epmc

Published In

Pigment Cell and Melanoma Research

Volume

26

Issue

3

Publish Date

2013

Start Page

422

End Page

425

DOI

10.1111/pcmr.12070

Murine double minute 2 (MDM2) oncoprotein and p14(ARF) tumor suppressor play pivotal roles in regulating p53 and function in the MAPK pathway, which is mutated frequently in differentiated thyroid carcinoma (DTC). We hypothesized that functional polymorphisms in the promoters of MDM2 and p14(ARF) contribute to the interindividual difference in predisposition to DTC.MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440 were genotyped in 303 patients with DTC and 511 cancer-free healthy controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).MDM2-rs2279744 and p14(ARF)-rs3731217 were associated with a significantly increased risk of DTC (MDM2-rs2279744: TT versus TG/GG; OR, 1.5; 95% CI, 1.1-2.0; p14(ARF)-rs3731217: TG/GG versus TT; OR, 1.7; 95% CI, 1.2-2.3). No association was found for MDM2-rs937283 or p14(ARF)-rs3088440. Individuals carrying 3-4 risk genotypes of MDM2 and p14(ARF) had 2.2 times (95% CI, 1.4-3.5) the risk for DTC of individuals carrying 0-1 risk genotypes (P trend = .021). The combined effect of MDM2 and p14(ARF) on risk of DTC was confined to young subjects (≤ 45 years), nonsmokers, nondrinkers, and subjects with a first-degree family history of cancer. These associations were quite similar in strength when cases were restricted to those with papillary thyroid cancer.Our results suggest that polymorphisms of MDM2 and p14(ARF) contribute to the interindividual difference in susceptibility to DTC, either alone or more likely jointly. The observed associations warrant further confirmation in independent studies.

Authors

Zhang, F; Xu, L; Wei, Q; Song, X; Sturgis, EM; Li, G

MLA Citation

Zhang, F, Xu, L, Wei, Q, Song, X, Sturgis, EM, and Li, G. "Significance of MDM2 and P14 ARF polymorphisms in susceptibility to differentiated thyroid carcinoma." Surgery 153.5 (May 2013): 711-717.

PMID

23218882

Source

epmc

Published In

Surgery

Volume

153

Issue

5

Publish Date

2013

Start Page

711

End Page

717

DOI

10.1016/j.surg.2012.11.009

Steroid 5-α-reductase type 2 (SRD5A2) V89L and A49T polymorphisms are thought to play a crucial role in the androgen synthesis and metabolic pathway, but their associations with prostate cancer risk remain controversial. To provide a more precise estimation of the associations between V89L and A49T polymorphisms and prostate cancer risk, we performed a meta-analysis using all published case-control studies of prostate cancer since January 1995. We used odds ratio (OR) and its 95% confidence interval (CI) to assess the strength of the association under various genetic models in both overall and stratified analyses. We also calculated the false-positive report probability, the power of the current study, and the observed P value for significant findings. This analysis included 45 eligible studies of a total of 15,562 cases and 15,385 controls, in which no significant associations were found for the V89L polymorphisms under all genetic models. However, small excess prostate cancer risk was associated with the 49T allele in mixed populations compared with the 49A allele (OR = 1.24, 95% CI = 1.02-1.50), and similar results were observed in Caucasians (OR = 1.24, 95% CI = 1.01-1.53). The sensitivity analysis further strengthened the validity of these findings without publication bias. Although there was no overall association between V89L and prostate cancer risk, A49T might play a role in the etiology of prostate cancer among Caucasians. Additional large and well-designed studies are warranted to validate these findings.

Authors

Li, Q; Zhu, Y; He, J; Wang, M; Zhu, M; Shi, T; Qiu, L; Ye, D; Wei, Q

MLA Citation

Li, Q, Zhu, Y, He, J, Wang, M, Zhu, M, Shi, T, Qiu, L, Ye, D, and Wei, Q. "Steroid 5-alpha-reductase type 2 (SRD5A2) V89L and A49T polymorphisms and sporadic prostate cancer risk: a meta-analysis." Molecular biology reports 40.5 (May 2013): 3597-3608.

PMID

23277398

Source

epmc

Published In

Molecular Biology Reports

Volume

40

Issue

5

Publish Date

2013

Start Page

3597

End Page

3608

DOI

10.1007/s11033-012-2434-x

PURPOSE: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. RESULTS: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. CONCLUSIONS: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

Authors

Pang, Q; Wei, Q; Xu, T; Yuan, X; Lopez Guerra, JL; Levy, LB; Liu, Z; Gomez, DR; Zhuang, Y; Wang, L-E; Mohan, R; Komaki, R; Liao, Z

MLA Citation

Pang, Q, Wei, Q, Xu, T, Yuan, X, Lopez Guerra, JL, Levy, LB, Liu, Z, Gomez, DR, Zhuang, Y, Wang, L-E, Mohan, R, Komaki, R, and Liao, Z. "Functional promoter variant rs2868371 of HSPB1 is associated with risk of radiation pneumonitis after chemoradiation for non-small cell lung cancer." International journal of radiation oncology, biology, physics 85.5 (April 2013): 1332-1339.

PMID

23374503

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

85

Issue

5

Publish Date

2013

Start Page

1332

End Page

1339

DOI

10.1016/j.ijrobp.2012.10.011

We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 × 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanoma-susceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.

Authors

Iles, MM; Law, MH; Stacey, SN; Han, J; Fang, S; Pfeiffer, R; Harland, M; Macgregor, S; Taylor, JC; Aben, KK; Akslen, LA; Avril, M-F; Azizi, E; Bakker, B; Benediktsdottir, KR; Bergman, W; Scarrà, GB; Brown, KM; Calista, D; Chaudru, V; Fargnoli, MC; Cust, AE; Demenais, F; de Waal, AC; Dębniak, T; Elder, DE; Friedman, E; Galan, P; Ghiorzo, P; Gillanders, EM; Goldstein, AM; Gruis, NA; Hansson, J; Helsing, P; Hočevar, M; Höiom, V; Hopper, JL; Ingvar, C; Janssen, M; Jenkins, MA; Kanetsky, PA et al.

MLA Citation

Iles, MM, Law, MH, Stacey, SN, Han, J, Fang, S, Pfeiffer, R, Harland, M, Macgregor, S, Taylor, JC, Aben, KK, Akslen, LA, Avril, M-F, Azizi, E, Bakker, B, Benediktsdottir, KR, Bergman, W, Scarrà, GB, Brown, KM, Calista, D, Chaudru, V, Fargnoli, MC, Cust, AE, Demenais, F, de Waal, AC, Dębniak, T, Elder, DE, Friedman, E, Galan, P, Ghiorzo, P, Gillanders, EM, Goldstein, AM, Gruis, NA, Hansson, J, Helsing, P, Hočevar, M, Höiom, V, Hopper, JL, Ingvar, C, Janssen, M, Jenkins, MA, and Kanetsky, PA et al. "A variant in FTO shows association with melanoma risk not due to BMI." Nature genetics 45.4 (April 2013): 428-432e1.

PMID

23455637

Source

epmc

Published In

Nature Genetics

Volume

45

Issue

4

Publish Date

2013

Start Page

428

End Page

432e1

DOI

10.1038/ng.2571

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.

Authors

Shi, T-Y; Cheng, X; Yu, K-D; Sun, M-H; Shao, Z-M; Wang, M-Y; Zhu, M-L; He, J; Li, Q-X; Chen, X-J; Zhou, X-Y; Wu, X; Wei, Q

MLA Citation

Shi, T-Y, Cheng, X, Yu, K-D, Sun, M-H, Shao, Z-M, Wang, M-Y, Zhu, M-L, He, J, Li, Q-X, Chen, X-J, Zhou, X-Y, Wu, X, and Wei, Q. "Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes." Carcinogenesis 34.4 (April 2013): 770-778.

PMID

23299407

Source

epmc

Published In

Carcinogenesis

Volume

34

Issue

4

Publish Date

2013

Start Page

770

End Page

778

DOI

10.1093/carcin/bgt001

Genome-wide association studies (GWASs) have mainly focused on top significant single nucleotide polymorphisms (SNPs), most of which did not have clear biological functions but were just surrogates for unknown causal variants. Studying SNPs with modest association and putative functions in biologically plausible pathways has become one complementary approach to GWASs. To unravel the key roles of mitogen-activated protein kinase (MAPK) pathways in cutaneous melanoma (CM) risk, we re-evaluated the associations between 47 818 SNPs in 280 MAPK genes and CM risk using our published GWAS dataset with 1804 CM cases and 1026 controls. We initially found 105 SNPs with P ≤ 0.001, more than expected by chance, 26 of which were predicted to be putatively functional SNPs. The risk associations with 16 SNPs around DUSP14 (rs1051849) and a previous reported melanoma locus MAFF/PLA2G6 (proxy SNP rs4608623) were replicated in the GenoMEL dataset (P < 0.01) but failed in the Australian dataset. Meta-analysis showed that rs1051849 in the 3' untranslated regions of DUSP14 was associated with a reduced risk of melanoma (odds ratio = 0.89, 95% confidence interval: 0.82-0.96, P = 0.003, false discovery rate = 0.056). Further genotype-phenotype correlation analysis using the 90 HapMap lymphoblastoid cell lines from Caucasians showed significant correlations between two SNPs (rs1051849 and rs4608623) and messenger RNA expression levels of DUSP14 and MAFF (P = 0.025 and P = 0.010, respectively). Gene-based tests also revealed significant SNPs were over-represented in MAFF, PLA2G6, DUSP14 and other 16 genes. Our results suggest that functional SNPs in MAPK pathways may contribute to CM risk. Further studies are warranted to validate our findings.

Authors

Liu, H; Wang, L-E; Liu, Z; Chen, WV; Amos, CI; Lee, JE; Q-MEGA and AMFS Investigators, ; GenoMEL Investigators, ; Iles, MM; Law, MH; Barrett, JH; Montgomery, GW; Taylor, JC; MacGregor, S; Cust, AE; Newton Bishop, JA; Hayward, NK; Bishop, DT; Mann, GJ; Affleck, P; Wei, Q

MLA Citation

Liu, H, Wang, L-E, Liu, Z, Chen, WV, Amos, CI, Lee, JE, Q-MEGA and AMFS Investigators, , GenoMEL Investigators, , Iles, MM, Law, MH, Barrett, JH, Montgomery, GW, Taylor, JC, MacGregor, S, Cust, AE, Newton Bishop, JA, Hayward, NK, Bishop, DT, Mann, GJ, Affleck, P, and Wei, Q. "Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk." Carcinogenesis 34.4 (April 2013): 885-892.

PMID

23291271

Source

epmc

Published In

Carcinogenesis

Volume

34

Issue

4

Publish Date

2013

Start Page

885

End Page

892

DOI

10.1093/carcin/bgs407

Caspases are important regulators and executioners in the apoptosis pathways and play crucial roles in carcinogenesis. We tested the hypothesis that functional variants of CASP genes are associated with risk of squamous cell carcinoma of the head and neck (SCCHN) and second primary malignancy (SPM). We genotyped 7 selected, potentially functional single nucleotide polymorphisms (SNPs) located in the microRNA binding sites of the 3' untranslational region (UTR; 2 in CASP3, 1 in CASP6, and 4 in CASP7) and evaluated their associations first with risk of SCCHN in 1066 patients with SCCHN and 1074 cancer-free control subjects and then with SPM in 846 patients in the same non-Hispanic white study population. We found that compared with the CASP3 TT genotype of rs1049253, the variant TC/CC genotypes were associated with significantly increased risk of SCCHN (adjusted odds ratio=1.29 and 95% confidence interval=1.07-1.56) and SPM (adjusted hazard ratio=1.79 and 95% CI=1.02-3.16) and worse SPM-free survival (log-rank P = 0.020), but no associations were found for the other 6 SNPs. We then performed additional experiments to seek functional relevance of the rs1049253 SNP. First, the luciferase activity and miR-885-5p mimic transfection tests suggested that CASP3 was the target of miR-885-5p and that rs1049253T>C resulted in altered regulation of the CASP3 expression. Second, the rs1049253 CC genotype was associated with reduced levels of CASP3 mRNA in peripheral blood mononuclear cells from 118 SCCHN patients and 103 cancer-free control subjects and lower levels of CASP3 protein expression in 11 head and neck cancer cell lines, compared with the TT genotype. Taken together, our data suggest that the miR-885-5p binding site rs1049253T>C SNP in the 3'-UTR of CASP3 modulates CASP3 expression at both mRNA and protein levels and thus contributes to SCCHN susceptibility.

Authors

Guan, X; Liu, Z; Liu, H; Yu, H; Wang, L-E; Sturgis, EM; Li, G; Wei, Q

MLA Citation

Guan, X, Liu, Z, Liu, H, Yu, H, Wang, L-E, Sturgis, EM, Li, G, and Wei, Q. "A functional variant at the miR-885-5p binding site of CASP3 confers risk of both index and second primary malignancies in patients with head and neck cancer." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27.4 (April 2013): 1404-1412.

PMID

23271051

Source

epmc

Published In

The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Volume

27

Issue

4

Publish Date

2013

Start Page

1404

End Page

1412

DOI

10.1096/fj.12-223420

A polymorphic pentanucleotide microsatellite sequence (TGYCC)n within the p53-inducible gene 3 (PIG3) promoter is correlated with the extent of transcriptional activation by p53 and thought to modulate susceptibility to cancer. Using a PCR-silver staining-based single-strand conformation assay, we visualized variant genotypes of the PIG3 promoter (TGYCC)n motif in a subset of 100 subjects for each of four ethnic groups: non-Hispanic whites, African Americans, Hispanic Americans and Native Chinese. We found that PIG3 (TGYCC)15 was the most common allele but less frequent in non-Hispanic whites (0.660) than in Chinese (0.785) (P = 0.016). In an additional study of 616 patients with squamous cell carcinoma of the head and neck (SCCHN) and 623 cancer-free controls in a non-Hispanic white population, we found that compared with those who were PIG3 (TGYCC)15 homozygotes, subjects without the PIG3 (TGYCC)15 allele had a significantly increased SCCHN risk [adjusted odds ratio (OR) = 1.34; 95% CI = 1.04-1.73 for heterozygotes and OR = 1.69; 95% CI = 1.18-2.44 for variant homozygotes] in an allele-dose response manner (P = 0.002). Consistently, subsequent luciferase reporter assay revealed that the wild-type (TGYCC)15 allele had the highest p53-mediated transcriptional activity, compared with the other (TGYCC)n motifs. Our data suggest that the PIG3 variant polymorphic repeats alleles other than (TGYCC)15 may affect p53 binding and thus may be a marker for susceptibility to SCCHN, but our findings need to be validated in larger studies.

Authors

Guan, X; Liu, Z; Wang, L; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Guan, X, Liu, Z, Wang, L, Wang, L-E, Sturgis, EM, and Wei, Q. "Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck." Carcinogenesis 34.4 (April 2013): 812-817.

PMID

23241165

Source

epmc

Published In

Carcinogenesis

Volume

34

Issue

4

Publish Date

2013

Start Page

812

End Page

817

DOI

10.1093/carcin/bgs388

To identify non-tumor biomarkers for prediction of tumor HPV status and prognosis of patients with squamous cell carcinoma of the oropharynx (SCCOP), we evaluated the association of single nucleotide polymorphisms (SNPs) in pre-miRNAs with HPV16 status and survival for SCCOP patients. We analyzed HPV16 status in tumor specimens and genotyped four SNPs in pre-miRNAs (hsa-mir-146a rs2910164 G>C, hsa-mir-149 rs2292832 G>T, hsa-mir-196a2 rs11614913 C>T, and hsa-mir-499 rs3746444 A>G) in 309 SCCOP patients. Unconditional logistic regression models were used for calculation of odds ratio (OR) and 95% confidence intervals (CIs), and Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate associations. We found that statistically significant associations with HPV16-positive SCCOP and survival were found for hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913, while such similar associations were not observed for hsa-mir-149 rs2292832 and hsa-mir499 rs3746444. Compared with those with corresponding hsa-mir-146a CG/CC and has-mir-196a2 CC genotypes, the hsa-mir-146a GG and hsa-mir-196a2 CT/TT wild-type genotypes were significantly associated with HPV16-positive tumor status (adjusted OR, 2.4; 95% CI, 1.4-4.1 and adjusted OR, 2.1, 95% CI, 1.2-3.6), respectively. Patients having hsa-mir-146a rs2910164 GG and hsa-mir196a2 rs11614913 CT/TT genotypes had significantly better overall, disease-specific, and disease-free survival compared with those having the corresponding CG/CC and CC genotypes, respectively. Furthermore, these genotypes were significantly associated with reduced risk of overall death, death owing to disease, and recurrence after adjustment for important prognostic confounders including HPV status, smoking, and stage. Our findings indicate pre-miRNA polymorphisms may predict tumor HPV16-positive SCCOP cases and may be prognostic biomarkers for SCCOP.

Authors

Guan, X; Sturgis, EM; Song, X; Liu, Z; El-Naggar, AK; Wei, Q; Li, G

MLA Citation

Guan, X, Sturgis, EM, Song, X, Liu, Z, El-Naggar, AK, Wei, Q, and Li, G. "Pre-microRNA variants predict HPV16-positive tumors and survival in patients with squamous cell carcinoma of the oropharynx." Cancer letters 330.2 (April 2013): 233-240.

PMID

23219900

Source

epmc

Published In

Cancer Letters

Volume

330

Issue

2

Publish Date

2013

Start Page

233

End Page

240

DOI

10.1016/j.canlet.2012.11.048

Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case-control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95% CI 1.08-1.49 and 1.04-1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.

Authors

Shi, T-Y; Zhu, M-L; He, J; Wang, M-Y; Li, Q-X; Zhou, X-Y; Sun, M-H; Shao, Z-M; Yu, K-D; Cheng, X; Wu, X; Wei, Q

MLA Citation

Shi, T-Y, Zhu, M-L, He, J, Wang, M-Y, Li, Q-X, Zhou, X-Y, Sun, M-H, Shao, Z-M, Yu, K-D, Cheng, X, Wu, X, and Wei, Q. "Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women." Human genetics 132.3 (March 2013): 301-312.

PMID

23180271

Source

epmc

Published In

Human Genetics

Volume

132

Issue

3

Publish Date

2013

Start Page

301

End Page

312

DOI

10.1007/s00439-012-1245-4

The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP).We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered.Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites.ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

Authors

Xiong, H; Liao, Z; Liu, Z; Xu, T; Wang, Q; Liu, H; Komaki, R; Gomez, D; Wang, L-E; Wei, Q

MLA Citation

Xiong, H, Liao, Z, Liu, Z, Xu, T, Wang, Q, Liu, H, Komaki, R, Gomez, D, Wang, L-E, and Wei, Q. "ATM polymorphisms predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy." International journal of radiation oncology, biology, physics 85.4 (March 2013): 1066-1073.

PMID

23154078

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

85

Issue

4

Publish Date

2013

Start Page

1066

End Page

1073

DOI

10.1016/j.ijrobp.2012.09.024

To determine the association between radiation doses delivered to the mandible and the occurrence of osteoradionecrosis (ORN).We reviewed the records of 402 oropharyngeal cancer patients with stage T1 or T2 disease treated with definitive radiation between January 2000 and October 2008 for the occurrence of ORN. Demographic and treatment variables were compared between patients with ORN and those without. To examine the dosimetric relationship further, a nested case-control comparison was performed. One to 2 ORN-free patients were selected to match each ORN patient by age, sex, radiation type, treatment year, and cancer subsite. Detailed radiation treatment plans for the ORN cases and matched controls were reviewed. Mann-Whitney test and conditional logistic regression were used to compare relative volumes of the mandible exposed to doses ranging from 10 Gy-60 Gy in 10-Gy increments.In 30 patients (7.5%), ORN developed during a median follow-up time of 31 months, including 6 patients with grade 4 ORN that required major surgery. The median time to develop ORN was 8 months (range, 0-71 months). Detailed radiation treatment plans were available for 25 of the 30 ORN patients and 40 matched ORN-free patients. In the matched case-control analysis, there was a statistically significant difference between the volumes of mandible in the 2 groups receiving doses between 50 Gy (V50) and 60 Gy (V60). The most notable difference was seen at V50, with a P value of .02 in the multivariate model after adjustment for the matching variables and dental status (dentate or with extraction).V50 and V60 saw the most significant differences between the ORN group and the comparison group. Minimizing the percent mandibular volume exposed to 50 Gy may reduce ORN risk.

Authors

Tsai, CJ; Hofstede, TM; Sturgis, EM; Garden, AS; Lindberg, ME; Wei, Q; Tucker, SL; Dong, L

MLA Citation

Tsai, CJ, Hofstede, TM, Sturgis, EM, Garden, AS, Lindberg, ME, Wei, Q, Tucker, SL, and Dong, L. "Osteoradionecrosis and radiation dose to the mandible in patients with oropharyngeal cancer." International journal of radiation oncology, biology, physics 85.2 (February 2013): 415-420.

PMID

22795804

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

85

Issue

2

Publish Date

2013

Start Page

415

End Page

420

DOI

10.1016/j.ijrobp.2012.05.032

BACKGROUND: MicroRNA (miRNA)-related single nucleotide polymorphisms (SNPs) may compromise miRNA binding affinity and modify mRNA expression levels of the target genes, thus leading to cancer susceptibility. However, few studies have investigated roles of miRNA-related SNPs in the etiology of cervical carcinoma. METHODS: In this case-control study of 1,584 cervical cancer cases and 1,394 cancer-free female controls, we investigated associations between two miR-218-related SNPs involved in the LAMB3-miR-218 pathway and the risk of cervical carcinoma in Eastern Chinese women. RESULTS: We found that the pri-miR-218 rs11134527 variant GG genotype was significantly associated with a decreased risk of cervical carcinoma compared with AA/AG genotypes (adjusted OR=0.77, 95% CI=0.63-0.95, P=0.015). However, this association was not observed for the miR-218 binding site SNP (rs2566) on LAMB3. Using the multifactor dimensionality reduction analysis, we observed some evidence of interactions of these two SNPs with other risk factors, especially age at primiparity and menopausal status, in the risk of cervical carcinoma. CONCLUSIONS: The pri-miR-218 rs11134527 SNP was significantly associated with the risk of cervical carcinoma in Eastern Chinese women. Larger, independent studies are warranted to validate our findings.

Authors

Shi, T-Y; Chen, X-J; Zhu, M-L; Wang, M-Y; He, J; Yu, K-D; Shao, Z-M; Sun, M-H; Zhou, X-Y; Cheng, X; Wu, X; Wei, Q

MLA Citation

Shi, T-Y, Chen, X-J, Zhu, M-L, Wang, M-Y, He, J, Yu, K-D, Shao, Z-M, Sun, M-H, Zhou, X-Y, Cheng, X, Wu, X, and Wei, Q. "A pri-miR-218 variant and risk of cervical carcinoma in Chinese women." BMC cancer 13 (January 15, 2013): 19-.

PMID

23320911

Source

epmc

Published In

BMC Cancer

Volume

13

Publish Date

2013

Start Page

19

DOI

10.1186/1471-2407-13-19

Suboptimal cellular DNA repair capacity (DRC) has been shown to be associated with enhanced cancer risk, but genetic variants affecting the DRC phenotype have not been comprehensively investigated. In this study, with the available DRC phenotype data, we analyzed correlations between the DRC phenotype and genotypes detected by the Illumina 317K platform in 1,774 individuals of European ancestry from a Texas lung cancer genome-wide association study. The discovery phase was followed by a replication in an independent set of 1,374 cases and controls of European ancestry. We applied a generalized linear model with single nucleotide polymorphisms as predictors and DRC (a continuous variable) as the outcome. Covariates of age, sex, pack-years of smoking, DRC assay-related variables, and case-control status of the study participants were adjusted in the model. We validated that reduced DRC was associated with an increased risk of lung cancer in both independent datasets. Several suggestive loci that contributed to the DRC phenotype were defined in ERCC2/XPD, PHACTR2, and DUSP1. In summary, we determined that DRC is an independent risk factor for lung cancer, and we defined several genetic loci contributing to DRC phenotype.

Authors

Wang, L-E; Gorlova, OY; Ying, J; Qiao, Y; Weng, S-F; Lee, AT; Gregersen, PK; Spitz, MR; Amos, CI; Wei, Q

MLA Citation

Wang, L-E, Gorlova, OY, Ying, J, Qiao, Y, Weng, S-F, Lee, AT, Gregersen, PK, Spitz, MR, Amos, CI, and Wei, Q. "Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer." Cancer research 73.1 (January 2013): 256-264.

PMID

23108145

Source

epmc

Published In

Cancer Research

Volume

73

Issue

1

Publish Date

2013

Start Page

256

End Page

264

DOI

10.1158/0008-5472.can-12-1915

To determine whether single-nucleotide polymorphisms (SNPs) in genes associated with DNA repair, cell cycle, transforming growth factor-β, tumor necrosis factor and receptor, folic acid metabolism, and angiogenesis can significantly improve the fit of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model of radiation pneumonitis (RP) risk among patients with non-small cell lung cancer (NSCLC).Sixteen SNPs from 10 different genes (XRCC1, XRCC3, APEX1, MDM2, TGFβ, TNFα, TNFR, MTHFR, MTRR, and VEGF) were genotyped in 141 NSCLC patients treated with definitive radiation therapy, with or without chemotherapy. The LKB model was used to estimate the risk of severe (grade≥3) RP as a function of mean lung dose (MLD), with SNPs and patient smoking status incorporated into the model as dose-modifying factors. Multivariate analyses were performed by adding significant factors to the MLD model in a forward stepwise procedure, with significance assessed using the likelihood-ratio test. Bootstrap analyses were used to assess the reproducibility of results under variations in the data.Five SNPs were selected for inclusion in the multivariate NTCP model based on MLD alone. SNPs associated with an increased risk of severe RP were in genes for TGFβ, VEGF, TNFα, XRCC1 and APEX1. With smoking status included in the multivariate model, the SNPs significantly associated with increased risk of RP were in genes for TGFβ, VEGF, and XRCC3. Bootstrap analyses selected a median of 4 SNPs per model fit, with the 6 genes listed above selected most often.This study provides evidence that SNPs can significantly improve the predictive ability of the Lyman MLD model. With a small number of SNPs, it was possible to distinguish cohorts with >50% risk vs <10% risk of RP when they were exposed to high MLDs.

Authors

Tucker, SL; Li, M; Xu, T; Gomez, D; Yuan, X; Yu, J; Liu, Z; Yin, M; Guan, X; Wang, L-E; Wei, Q; Mohan, R; Vinogradskiy, Y; Martel, M; Liao, Z

MLA Citation

Tucker, SL, Li, M, Xu, T, Gomez, D, Yuan, X, Yu, J, Liu, Z, Yin, M, Guan, X, Wang, L-E, Wei, Q, Mohan, R, Vinogradskiy, Y, Martel, M, and Liao, Z. "Incorporating single-nucleotide polymorphisms into the Lyman model to improve prediction of radiation pneumonitis." International journal of radiation oncology, biology, physics 85.1 (January 2013): 251-257.

PMID

22541966

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

85

Issue

1

Publish Date

2013

Start Page

251

End Page

257

DOI

10.1016/j.ijrobp.2012.02.021

REV3Lp, the catalytic subunit of DNA polymerase zeta, is the major participant in translesion DNA synthesis. Recent evidence suggests that REV3L has an important role in the maintenance of genome stability despite its mutagenic characteristics. Such a function makes it a cancer susceptibility candidate gene. To investigate association between REV3L polymorphisms and lung cancer risk in a Chinese population, we first genotyped 15 common polymorphisms of the REV3L gene and found that three single nucleotide polymorphisms (rs465646, rs459809 and rs1002481) were significantly associated with lung cancer risk. One of the strongest associations observed was for the 3'-terminal untranslated region (3'UTR) 460 T>C polymorphism (rs465646) (adjusted odds ratio (OR)=0.69 for TC/CC; P=0.007, compared with TT). Similar results were obtained in a subsequent replication study (adjusted OR=0.72; P=0.016). Combined data from the two studies of 1072 lung cancer patients and 1064 cancer-free controls generated an even stronger association (adjusted OR=0.71; P=3.04 × 10(-4)). This 3'UTR 460 T>C variant was predicted to modulate the binding of several micro RNAs. Surface plasmon resonance analysis and luciferase assays showed that the T allele demonstrated a stronger binding affinity for miR-25 and miR-32, resulting in significantly weaker reporter expression levels. Additional experiments revealed that miR-25/32 could downregulate endogenous REV3L. Furthermore, the tumor-suppressing role of REV3L was confirmed by the foci formation assay. These results support our hypothesis that the REV3L rs465646 variant modifies lung cancer susceptibility in Chinese Han population by affecting miRNA-mediated gene regulation.

Authors

Zhang, S; Chen, H; Zhao, X; Cao, J; Tong, J; Lu, J; Wu, W; Shen, H; Wei, Q; Lu, D

MLA Citation

Zhang, S, Chen, H, Zhao, X, Cao, J, Tong, J, Lu, J, Wu, W, Shen, H, Wei, Q, and Lu, D. "REV3L 3'UTR 460 T>C polymorphism in microRNA target sites contributes to lung cancer susceptibility." Oncogene 32.2 (January 2013): 242-250.

PMID

22349819

Source

epmc

Published In

Oncogene: Including Oncogene Reviews

Volume

32

Issue

2

Publish Date

2013

Start Page

242

End Page

250

DOI

10.1038/onc.2012.32

Transforming growth factor (TGF) -β1 signaling is involved in cancer-cell metastasis. We investigated whether single nucleotide polymorphisms (SNPs) at TGFβ1 were associated with overall survival (OS) and distant metastasis-free survival (DMFS) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy, with or without chemotherapy.We genotyped TGFβ1 SNPs at rs1800469 (C-509T), rs1800471 (G915C), and rs1982073 (T+29C) by polymerase chain reaction-restriction fragment length polymorphism in blood samples from 205 NSCLC patients who had had definitive radiotherapy at one institution in November 1998-January 2005. We also tested whether the TGF-β1 rs1982073 (T+29C) SNP affected the migration and invasion of A549 and PC9 lung cancer cells.Median follow-up time for all patients was 17 months (range, 1-97 months; 39 months for patients alive at the time of analysis). Multivariate analysis showed that the TGFβ1 rs1800469 CT/CC genotype was associated with poor OS (hazard ratio [HR] = 1.463 [95% confidence interval {CI} = 1.012-2.114], P = 0.043) and shorter DMFS (HR = 1.601 [95% CI = 1.042-2.459], P = 0.032) and that the TGFβ1 rs1982073 CT/CC genotype predicted poor DMFS (HR = 1.589 [95% CI = 1.009-2.502], P = 0.046) and poor brain MFS (HR = 2.567 [95% CI = 1.155-5.702], P = 0.021) after adjustment for age, sex, race, performance status, smoking status, tumor histology and volume, stage, receipt of concurrent radiochemotherapy, number of chemotherapy cycles, and radiation dose. Transfection with TGFβ1+29C (vs. +29T) stimulated the migration and invasion of A549 and PC9 cells, suggesting that TGFβ1+29C may be linked with increased metastatic potential.TGFβ1 genotypes at rs1800469 and rs1982073 could be useful for predicting DMFS among patients with NSCLC treated with definitive radiation therapy. These findings require validation in larger prospective trials and thorough mechanistic studies.

Authors

Yuan, X; Wei, Q; Komaki, R; Liu, Z; Yang, J; Tucker, SL; Xu, T; Heymach, JV; Lu, C; Cox, JD; Liao, Z

MLA Citation

Yuan, X, Wei, Q, Komaki, R, Liu, Z, Yang, J, Tucker, SL, Xu, T, Heymach, JV, Lu, C, Cox, JD, and Liao, Z. "TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy." PloS one 8.6 (January 2013): e65659-.

PMID

23840350

Source

epmc

Published In

PloS one

Volume

8

Issue

6

Publish Date

2013

Start Page

e65659

DOI

10.1371/journal.pone.0065659

Both microRNAs and human papillomavirus (HPV) infection play an important role in the development and progression of oral squamous cell carcinoma (OSCC). In addition, microRNAs affect all facets of the immune/inflammation responses to infection, which may control HPV clearance. We thus hypothesized that microRNA polymorphisms modify the association between HPV16 seropositivity and OSCC risk.Four single-nucleotide polymorphisms in microRNAs were genotyped and HPV16 serology was determined in 325 cases and 335 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariable logistic regression models.Overall, each polymorphism had no significant main effect on OSCC risk. Compared with the risk among individuals with both miR146 rs2910164 GG genotype and HPV16 seronegativity, risk of OSCC was increased among those with CG or CC genotype and HPV16 seronegativity (OR, 1.2; 95% CI, 0.9-1.8), GG genotype and HPV16 seropositivity (OR, 3.0; 95% CI, 1.8-5.0), and CG or CC genotype and HPV16 seropositivity (OR, 4.7; 95% CI, 2.3-9.4). Similar results were found for miR149 rs2292832, miR196 rs11614913, and miR499 rs3746444. Analyses stratified by tumor sites and smoking status showed that each polymorphism significantly increased the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly prominent in never smokers.Our results indicate that microRNA polymorphisms modify the risk of OSCC associated with HPV16 seropositivity, particularly in patients with SCCOP and never smokers. Larger studies are needed to verify our findings.

Authors

Song, X; Sturgis, EM; Liu, J; Jin, L; Wang, Z; Zhang, C; Wei, Q; Li, G

MLA Citation

Song, X, Sturgis, EM, Liu, J, Jin, L, Wang, Z, Zhang, C, Wei, Q, and Li, G. "MicroRNA variants increase the risk of HPV-associated squamous cell carcinoma of the oropharynx in never smokers." PloS one 8.2 (January 2013): e56622-.

PMID

23457596

Source

epmc

Published In

PloS one

Volume

8

Issue

2

Publish Date

2013

Start Page

e56622

DOI

10.1371/journal.pone.0056622

PURPOSE: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair pathway that effectively repairs DNA damage induced by chemotherapeutic agents. Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could have an impact on clinical outcomes in cancer patients who received chemotherapy. However, few studies have simultaneously investigated the roles of ERCC1 and ERCC2 SNPs in clinical outcomes in gastric cancer patients. EXPERIMENTAL DESIGN: We genotyped by the TaqMan assay three common, potentially functional ERCC1 (rs3212986) and ERCC2 SNPs (rs13181 and rs1799793) in 360 gastric cancer patients. We used both Kaplan-Meier tests and Cox proportional hazards models to evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical outcomes. RESULTS: We found that, compared with ERCC2 rs1799793 GG+AG genotypes, the homozygous variant AA genotype was associated with significantly poorer overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to 3.56; P=0.004). In combined analyses, patients with any one of the three unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793 AA) had statistically significant hazards of poor prognosis (Adjusted HR, 1.54; 95% CI, 1.06 to 2.25; P=0.025), compared with those without any unfavorable genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986) had a significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011), compared with the common haplotype G-T-G. CONCLUSION: ERCC1 and ERCC2 functional SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large prospective studies are essential to confirm our findings.

Authors

Li, Y; Liu, Z; Liu, H; Wang, L-E; Tan, D; Ajani, JA; Wei, Q-Y

MLA Citation

Li, Y, Liu, Z, Liu, H, Wang, L-E, Tan, D, Ajani, JA, and Wei, Q-Y. "ERCC1 and ERCC2 variants predict survival in gastric cancer patients." PloS one 8.9 (January 2013): e71994-.

PMID

24023723

Source

epmc

Published In

PloS one

Volume

8

Issue

9

Publish Date

2013

Start Page

e71994

DOI

10.1371/journal.pone.0071994

BACKGROUND: Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer. METHODS: In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis. RESULTS: In the single-locus analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under a recessive model, compared with the CT/CC genotypes. In the combined analysis of all four SNPs, we found that the risk of gastric cancer decreased by 19% in those carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68-0.96), compared with those carrying zero risk genotypes, and this risk was more evident in subgroups of younger age (<59 years), females, non-smokers, non-drinkers and patients with non-gastric cardia adenocarcinoma. Further MDR analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSIONS: Potentially functional CASP7 variants may contribute to risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

Authors

Wang, M-Y; Zhu, M-L; He, J; Shi, T-Y; Li, Q-X; Wang, Y-N; Li, J; Zhou, X-Y; Sun, M-H; Wang, X-F; Yang, Y-J; Wang, J-C; Jin, L; Wei, Q-Y

MLA Citation

Wang, M-Y, Zhu, M-L, He, J, Shi, T-Y, Li, Q-X, Wang, Y-N, Li, J, Zhou, X-Y, Sun, M-H, Wang, X-F, Yang, Y-J, Wang, J-C, Jin, L, and Wei, Q-Y. "Potentially functional polymorphisms in the CASP7 gene contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population." PloS one 8.9 (January 2013): e74041-.

PMID

24040159

Source

epmc

Published In

PloS one

Volume

8

Issue

9

Publish Date

2013

Start Page

e74041

DOI

10.1371/journal.pone.0074041

BACKGROUND: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. METHODS: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. RESULTS: The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. CONCLUSIONS: Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.

Authors

He, J; Xi, B; Ruiter, R; Shi, T-Y; Zhu, M-L; Wang, M-Y; Li, Q-X; Zhou, X-Y; Qiu, L-X; Wei, Q-Y

MLA Citation

He, J, Xi, B, Ruiter, R, Shi, T-Y, Zhu, M-L, Wang, M-Y, Li, Q-X, Zhou, X-Y, Qiu, L-X, and Wei, Q-Y. "Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis." PloS one 8.10 (January 2013): e75135-.

PMID

24146750

Source

epmc

Published In

PloS one

Volume

8

Issue

10

Publish Date

2013

Start Page

e75135

DOI

10.1371/journal.pone.0075135

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

Authors

Fang, S; Han, J; Zhang, M; Wang, L-E; Wei, Q; Amos, CI; Lee, JE

MLA Citation

Fang, S, Han, J, Zhang, M, Wang, L-E, Wei, Q, Amos, CI, and Lee, JE. "Joint effect of multiple common SNPs predicts melanoma susceptibility." PloS one 8.12 (January 2013): e85642-.

PMID

24392023

Source

epmc

Published In

PloS one

Volume

8

Issue

12

Publish Date

2013

Start Page

e85642

DOI

10.1371/journal.pone.0085642

TNFAIP2 is a crucial gene involved in apoptosis. Single nucleotide polymorphisms (SNPs) in its miRNA binding sites could modulate functions of the miRNA-target genes and thus risk of cancers. In this study, we investigated associations between potentially functional SNPs in the miRNA binding sites of the 3'UTR of TNFAIP2 and gastric cancer risk in a US population.We conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. We genotyped four selected TNFAIP2 SNPs (rs8126 T>C, rs710100 G>A, rs1052912 G>A and rs1052823 G>T) and used the logistic regression analysis to assess associations of these SNPs with cancer risk.The rs8126 CC genotype was associated with a significantly elevated risk of gastric cancer (adjusted OR = 2.00, 95% CI = 1.09-3.64 and P = 0.024), compared with the combined rs8126 TT+TC genotypes, particularly in current drinkers. However, none of other TNFAIP2 SNPs was associated with risk of gastric cancer.Our data suggested that the TNFAIP2 miRNA binding site rs8126 T>C SNP may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies.

Authors

Xu, Y; Ma, H; Yu, H; Liu, Z; Wang, L-E; Tan, D; Muddasani, R; Lu, V; Ajani, JA; Wang, Y; Wei, Q

MLA Citation

Xu, Y, Ma, H, Yu, H, Liu, Z, Wang, L-E, Tan, D, Muddasani, R, Lu, V, Ajani, JA, Wang, Y, and Wei, Q. "The miR-184 binding-site rs8126 T>C polymorphism in TNFAIP2 is associated with risk of gastric cancer." PloS one 8.5 (January 2013): e64973-.

PMID

23724109

Source

epmc

Published In

PloS one

Volume

8

Issue

5

Publish Date

2013

Start Page

e64973

DOI

10.1371/journal.pone.0064973

The production of pigment by melanocytes tans the skin and protects against skin cancers. UV-exposed keratinocytes secrete α-MSH, which then activates melanin formation in melanocytes by inducing the microphthalmia-associated transcription factor (MITF). We show that PPAR-γ coactivator (PGC)-1α and PGC-1β are critical components of this melanogenic system in melanocytes. α-MSH signaling strongly induces PGC-1α expression and stabilizes both PGC-1α and PGC-1β proteins. The PGC-1s in turn activate the MITF promoter, and their expression correlates strongly with that of MITF in human melanoma cell lines and biopsy specimens. Inhibition of PGC-1α and PGC-1β blocks the α-MSH-mediated induction of MITF and melanogenic genes. Conversely, overexpression of PGC-1α induces pigment formation in cell culture and transgenic animals. Finally, polymorphism studies reveal expression quantitative trait loci in the PGC-1β gene that correlate with tanning ability and protection from melanoma in humans. These data identify PGC-1 coactivators as regulators of human tanning.

Authors

Shoag, J; Haq, R; Zhang, M; Liu, L; Rowe, GC; Jiang, A; Koulisis, N; Farrel, C; Amos, CI; Wei, Q; Lee, JE; Zhang, J; Kupper, TS; Qureshi, AA; Cui, R; Han, J; Fisher, DE; Arany, Z

MLA Citation

Shoag, J, Haq, R, Zhang, M, Liu, L, Rowe, GC, Jiang, A, Koulisis, N, Farrel, C, Amos, CI, Wei, Q, Lee, JE, Zhang, J, Kupper, TS, Qureshi, AA, Cui, R, Han, J, Fisher, DE, and Arany, Z. "PGC-1 coactivators regulate MITF and the tanning response." Molecular cell 49.1 (January 2013): 145-157.

PMID

23201126

Source

epmc

Published In

Molecular Cell

Volume

49

Issue

1

Publish Date

2013

Start Page

145

End Page

157

DOI

10.1016/j.molcel.2012.10.027

BACKGROUND: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. CONCLUSIONS/SIGNIFICANCES: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13-1.78), P = 0.003 and 1.29 (1.07-1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64-0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04-1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.

Authors

Li, Q; Gu, C; Zhu, Y; Wang, M; Yang, Y; Wang, J; Jin, L; Zhu, M-L; Shi, T-Y; He, J; Zhou, X; Ye, D-W; Wei, Q

MLA Citation

Li, Q, Gu, C, Zhu, Y, Wang, M, Yang, Y, Wang, J, Jin, L, Zhu, M-L, Shi, T-Y, He, J, Zhou, X, Ye, D-W, and Wei, Q. "Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population." PloS one 8.8 (January 2013): e71968-.

PMID

23940798

Source

epmc

Published In

PloS one

Volume

8

Issue

8

Publish Date

2013

Start Page

e71968

DOI

10.1371/journal.pone.0071968

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC+CC genotypes were associated with significantly increased GC risk (adjusted OR=1.52, 95% CI=1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR=0.68, 95% CI=0.48-0.97), compared with CC+CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted Ptrend=0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies. © 2013 Wiley Periodicals, Inc.

Authors

Wang, Q; Liu, H; Xiong, H; Liu, Z; Wang, L-E; Qian, J; Muddasani, R; Lu, V; Tan, D; Ajani, JA; Wei, Q

MLA Citation

Wang, Q, Liu, H, Xiong, H, Liu, Z, Wang, L-E, Qian, J, Muddasani, R, Lu, V, Tan, D, Ajani, JA, and Wei, Q. "Polymorphisms at the microRNA binding-site of the stem cell marker gene CD133 modify susceptibility to and survival of gastric cancer (Accepted)." Molecular Carcinogenesis (2013).

Website

http://hdl.handle.net/10161/10665

Source

scopus

Published In

Molecular Carcinogenesis

Publish Date

2013

DOI

10.1002/mc.22113

Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A>G, rs16430 6bp>0bp, and rs1059394 C>T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤55. We found that carriers of the rs16430 0bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR)=1.37, 95% confidence interval (CI): 1.08-1.73; P=0.010], compared with carriers of the 6bp/6bp genotype. This increased risk was more evident in older subjects (OR=1.47, 95% CI=1.06-2.03, P=0.022), never smokers (OR=1.67, 95% CI=1.23-2.25, P<0.001), never drinkers (OR=1.44, 95% CI=1.01-2.05, P=0.043), and estrogen receptor-positive patients (OR=1.46, 95% CI=1.11-1.92, P=0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0bp allele had a decrease in both luciferase activity by ∼70% and mRNA levels by ∼50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤55yr. Further validation in large population-based or cohort studies is needed. © 2013 Wiley Periodicals, Inc.

Authors

Guan, X; Liu, H; Ju, J; Li, Y; Li, P; Wang, L-E; Brewster, AM; Buchholz, TA; Arun, BK; Wei, Q; Liu, Z

MLA Citation

Guan, X, Liu, H, Ju, J, Li, Y, Li, P, Wang, L-E, Brewster, AM, Buchholz, TA, Arun, BK, Wei, Q, and Liu, Z. "Genetic variant rs16430 6bp>0bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-hispanic white women aged ≤55years (Accepted)." Molecular Carcinogenesis (2013).

Source

scopus

Published In

Molecular Carcinogenesis

Publish Date

2013

DOI

10.1002/mc.22097

Nucleotide excision repair (NER) recognizes and removes bulky DNA damage that leads to DNA double-helix distortion. Inherited defects in the NER pathway have been associated with aging symptoms and premature death. In this review, we discussed the mechanisms of how NER maintains genomic integrity and affects clinical outcomes, if NER is compromised, and the role of NER as a potential causative factor for mammalian aging. We summarized current evidence of the association between NER and aging process through a discussion of most updated research findings from genetic models of mice and molecular epidemiological studies from humans. Several possible mechanisms by which NER influences aging are suggested, including the GH/IGF1 axis, p53-induced apoptosis/senescence in response to DNA damage, reactive oxygen species (ROS), and maintenance of telomerase activities. A comparison between normal aging and NER deficiency-related aging is also made to illustrate their similarities and discrepancies. We conclude with a number of issues needed to be resolved to further clarify the relationship between NER and aging process in humans. © 2010 Nova Science Publishers, Inc. All rights reserved.

Authors

Yin, M; Wei, Q

MLA Citation

Yin, M, and Wei, Q. "Nucleotide-excision repair deficiency: Acausative factor for accelerated aging diseases in humans?." (December 1, 2012): 205-222. (Chapter)

Source

scopus

Publish Date

2012

Start Page

205

End Page

222

We investigated the association between single nucleotide polymorphisms (SNPs) in the transforming growth factor β1 (TGFβ1) gene and the risk of radiation-induced esophageal toxicity (RE) in patients with non-small-cell lung cancer (NSCLC).Ninety-seven NSCLC patients with available genomic DNA samples and mostly treated with intensity modulated radio(chemo)therapy from 2003 to 2006 were used as a test dataset and 101 NSCLC patients treated with 3-dimensional conformal radio(chemo)therapy from 1998 to 2002 were used as a validation set. We genotyped three SNPs of the TGFβ1 gene (rs1800469:C-509T, rs1800471:G915C, and rs1982073:T869C) by the polymerase chain reaction restriction fragment length polymorphism method.In the test dataset, the CT/TT genotypes of TGFβ1 rs1800469:C-509T were associated with a statistically significant higher risk of RE grade⩾3 in univariate (P=0.026) and multivariate analysis (P=0.045) when compared with the CC genotype. These results were again observed in both univariate (P=0.045) and multivariate (P=0.023) analysis in the validation dataset.We found and validated that the TGFβ1 rs1800469:C-509T genotype is associated with severe RE. This response marker may be used for guiding therapy intensity in an individual patient, which would further the goal of individualized therapy.

Authors

Guerra, JLL; Gomez, D; Wei, Q; Liu, Z; Wang, L-E; Yuan, X; Zhuang, Y; Komaki, R; Liao, Z

MLA Citation

Guerra, JLL, Gomez, D, Wei, Q, Liu, Z, Wang, L-E, Yuan, X, Zhuang, Y, Komaki, R, and Liao, Z. "Association between single nucleotide polymorphisms of the transforming growth factor β1 gene and the risk of severe radiation esophagitis in patients with lung cancer." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 105.3 (December 2012): 299-304.

PMID

23022171

Source

epmc

Published In

Radiotherapy & Oncology

Volume

105

Issue

3

Publish Date

2012

Start Page

299

End Page

304

DOI

10.1016/j.radonc.2012.08.014

Deregulated expression of most members of the E2F family has been detected in many human cancers. We examined the association of common single nucleotide polymorphisms (SNPs) of E2F transcription factors 1 and 2 (E2F1 and E2F2) with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,096 SCCHN patients and 1,090 cancer-free controls. We genotyped 10 selected SNPs in E2F1 and E2F2, including those at the near 5'-untranslated region (UTR), microRNA (miRNA)-binding sites at the near 3'-UTR and tagSNPs according to bioinformatics analysis. Although none of the selected SNPs alone was significantly associated with risk of SCCHN, there was a statistically significantly increased risk of SCCHN associated with the combined risk genotypes (i.e., rs3213182 AA, rs3213183 GG, rs3213180 GG, rs321318121 GG, rs2742976 GT+TT, rs6667575 GA+AA, rs3218203 CC, rs3218148 AA, rs3218211 CC, and rs3218123 GT+TT). Compared with those with 0-4 risk genotypes, an increased risk was observed for those who carried 5-8 risk genotypes (adjusted OR = 1.04; 95% CI = 0.86-1.26) and 9-10 risk genotypes (adjusted OR = 1.62; 95% CI = 1.14-2.30) in a dose-response manner (P = 0.045). Furthermore, the joint effect was more pronounced among patients with oropharyngeal cancer, younger adults (≤57 yr old), men, non-smokers, non-drinkers, and individuals with family history of cancer in first-degree relatives. Additionally, we also observed that those with 5-10 risk genotypes had an earlier SCCHN onset than those with 0-4 risk genotypes, particularly for non-smokers and/or non-drinkers. We concluded that E2F1 and E2F2 genetic variants may jointly play important roles in head and neck carcinogenesis.

Authors

Lu, M; Liu, Z; Yu, H; Wang, L-E; Li, G; Sturgis, EM; Johnson, DG; Wei, Q

MLA Citation

Lu, M, Liu, Z, Yu, H, Wang, L-E, Li, G, Sturgis, EM, Johnson, DG, and Wei, Q. "Combined effects of E2F1 and E2F2 polymorphisms on risk and early onset of squamous cell carcinoma of the head and neck." Molecular carcinogenesis 51 Suppl 1 (October 2012): E132-E141.

PMID

22344756

Source

epmc

Published In

Molecular Carcinogenesis

Volume

51 Suppl 1

Publish Date

2012

Start Page

E132

End Page

E141

DOI

10.1002/mc.21882

P53 up-regulated modulator of apoptosis (PUMA) is a critical factor in the intrinsic apoptotic pathway. Through PUMA-dependent mechanisms, human papillomavirus 16 (HPV16) oncoprotein may affect apoptosis by E6-mediated p53 degradation. To examine whether the PUMA variants modify the association between HPV16 serology and risk of squamous cell carcinoma of the head and neck (SCCHN), we genotyped two polymorphisms in the PUMA promoter (rs3810294 and rs2032809) in 380 cases and 335 cancer-free controls of non-Hispanic Whites, who were frequency-matched by age (±5 yr), sex, smoking, and drinking status. We found that each individual polymorphism had only a modest impact on risk of SCCHN, particularly in oropharyngeal cancer for rs3810294 and non-oropharyngeal cancer for rs2032809. After we stratified the individuals by HPV16 serology, and used those with the corresponding common homozygous genotype and HPV16 seronegativity as the reference group, for each polymorphism we found that the risk of SCCHN associated with HPV16 seropositivity was higher among those with variant genotypes than those with the corresponding common homozygous genotype. Notably, this effect modification was particularly pronounced in several subgroups including never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Furthermore, we also characterized the functional relevance of the two polymorphisms to explore the genotype-phenotype correlation. Our results suggested that the PUMA promoter polymorphisms may be a biomarker for risk of HPV16-associated SCCHN, particularly in never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.

Authors

Zhou, Z; Sturgis, EM; Liu, Z; Wang, L-E; Wei, Q; Li, G

MLA Citation

Zhou, Z, Sturgis, EM, Liu, Z, Wang, L-E, Wei, Q, and Li, G. "Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16-associated squamous cell carcinoma of the head and neck." Molecular carcinogenesis 51 Suppl 1 (October 2012): E54-E64.

PMID

22086558

Source

epmc

Published In

Molecular Carcinogenesis

Volume

51 Suppl 1

Publish Date

2012

Start Page

E54

End Page

E64

DOI

10.1002/mc.21838

We investigated potential associations between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and overall survival in US patients with non-small cell lung cancer (NSCLC).Using available genomic DNA samples from 224 patients with NSCLC treated with definitive radio(chemo)therapy, we genotyped 2 SNPs of HSPB1 (NCBI SNP nos. rs2868370 and rs2868371). We used both Kaplan-Meier cumulative probability and Cox proportional hazards analyses to evaluate the effect of HSPB1 genotypes on survival.Our cohort consisted of 117 men and 107 women, mostly white (79.5%), with a median age of 70 years. The median radiation dose was 66 Gy (range, 63-87.5 Gy), and 183 patients (82%) received concurrent platinum-based chemotherapy. The most common genotype of the rs2868371 SNP was CC (61%). Univariate and multivariate analyses showed that this genotype was associated with poorer survival than CG and GG genotypes (univariate hazard ratio [HR] = 1.39, 95% confidence interval [CI], 1.02-1.90; P=.037; multivariate HR = 1.39; 95% CI, 1.01-1.92; P=.045).Our results showed that the CC genotype of HSPB1 rs2868371 was associated with poorer overall survival in patients with NSCLC after radio(chemo)therapy, findings that contradict those of a previous study of Chinese patients. Validation of our findings with larger numbers of similar patients is needed, as are mechanical and clinical studies to determine the mechanism underlying these associations.

Authors

Xu, T; Wei, Q; Lopez Guerra, JL; Wang, L-E; Liu, Z; Gomez, D; O'Reilly, M; Lin, SH; Zhuang, Y; Levy, LB; Mohan, R; Zhou, H; Liao, Z

MLA Citation

Xu, T, Wei, Q, Lopez Guerra, JL, Wang, L-E, Liu, Z, Gomez, D, O'Reilly, M, Lin, SH, Zhuang, Y, Levy, LB, Mohan, R, Zhou, H, and Liao, Z. "HSPB1 gene polymorphisms predict risk of mortality for US patients after radio(chemo)therapy for non-small cell lung cancer." International journal of radiation oncology, biology, physics 84.2 (October 2012): e229-e235.

PMID

22608953

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

84

Issue

2

Publish Date

2012

Start Page

e229

End Page

e235

DOI

10.1016/j.ijrobp.2012.03.032

The insulin-like growth factor (IGF) pathway is believed to play a pivotal role in thyroid carcinogenesis. Polymorphisms of IGF-1 and IGF binding protein-3 (IGFBP-3) have been associated with modulation of risk for the emergence of assorted common malignancies, but studies of the influence of such polymorphisms on risk of differentiated thyroid carcinoma (DTC) are lacking. In a case-control study of 173 DTC patients, 101 patients with benign thyroid disease, and 401 controls, an unconditional logistical regression model adjusted for age and sex was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between polymorphisms of IGF-1 and IGFBP-3 and DTC risk. IGFBP-3 rs2132572 GA/AA genotypes were associated with a decreased risk of DTC (adjusted OR = 0.6, 95% CI: 0.4-0.9), particularly multifocal DTC (adjusted OR = 0.3, 95% CI: 0.1-0.7). The association with DTC was more evident in subjects with a first-degree family history of cancer (adjusted OR = 0.4, 95% CI: 0.2-0.7, P(interaction)  = 0.013) and non-drinkers (adjusted OR = 0.4, 95% CI: 0.2-0.7, P(interaction)  = 0.028). A four single nucleotide polymorphism haplotype of IGFBP-3 was associated with a decreased risk of DTC (adjusted OR = 0.7, 95% CI: 0.5-1.0, P = 0.030). Our study suggests that polymorphic IGFBP-3 may be involved in susceptibility to DTC.

Authors

Xu, L; Mugartegui, L; Li, G; Sarlis, NJ; Wei, Q; Zafereo, ME; Sturgis, EM

MLA Citation

Xu, L, Mugartegui, L, Li, G, Sarlis, NJ, Wei, Q, Zafereo, ME, and Sturgis, EM. "Functional polymorphisms in the insulin-like binding protein-3 gene may modulate susceptibility to differentiated thyroid carcinoma in Caucasian Americans." Molecular carcinogenesis 51 Suppl 1 (October 2012): E158-E167.

PMID

22415807

Source

epmc

Published In

Molecular Carcinogenesis

Volume

51 Suppl 1

Publish Date

2012

Start Page

E158

End Page

E167

DOI

10.1002/mc.21900

Matrix metallopeptidases (MMPs) play an important role in central nervous system tumor growth, invasion and spreading. The currently available data provide clear evidence for the involvement of MMP3 in the pathophysiology of glioma. The study aims to explore the association of single nucleotide polymorphisms (SNPs) across the MMP3 gene with glioma risk. Three haplotype tagging and additional two promoter SNPs were genotyped among 766 glioma patients and 824 cancer-free controls from East China. None of these polymorphisms alone had a significant effect on risk of gliomas. However, when three promoter polymorphisms were evaluated together by the number of putative risk of genotypes (i.e., rs645419AA, 632478CA+AA, rs522616AA), a statistically significantly increased risk of gliomas was associated with the combined genotypes with two to three risk genotypes, compared with those with zero to one risk genotypes (adjusted odds ratio (OR) = 1.32; 95% confidence interval (CI) = 1.03-1.68). This increased risk was also more pronounced among adults (adjusted OR = 1.14, 95%CI = 1.02-1.27), males (adjusted OR = 1.19, 95%CI = 1.05-1.36), smokers (adjusted OR = 1.28, 95%CI = 1.07-1.52), subjects with no family history of cancer (adjusted OR = 1.21, 95%CI = 1.07-1.37), and patients with nonastrocytic gliomas (adjusted OR = 1.23, 95%CI = 1.06-1.43). In summary, our results suggest that any one of MMP3 variants may not have a substantial effect on glioma risk, but a joint effect of MMP3 promoter polymorphisms may contribute to risk of gliomas, particularly for adult gliomas.

Authors

Fan, W; Zhou, K; Hu, D; Song, X; Zhao, Y; Chen, H; Wei, Q; Chen, G; Shi, J; Du, G; Mao, Y; Lu, D; Zhou, L

MLA Citation

Fan, W, Zhou, K, Hu, D, Song, X, Zhao, Y, Chen, H, Wei, Q, Chen, G, Shi, J, Du, G, Mao, Y, Lu, D, and Zhou, L. "Single nucleotide polymorphisms of matrix metallopeptidase 3 and risk of gliomas in a Chinese Han population." Molecular carcinogenesis 51 Suppl 1 (October 2012): E1-10.

PMID

21853476

Source

epmc

Published In

Molecular Carcinogenesis

Volume

51 Suppl 1

Publish Date

2012

Start Page

E1

End Page

10

DOI

10.1002/mc.20842

CASP7 plays a crucial role in cancer development and chemotherapy efficacy. We, therefore, explored whether single nucleotide polymorphisms (SNPs) of the CASP7 gene can modulate outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy.We systematically genotyped 17 SNPs of CASP7 first in a discovery set of 279 patients with advanced NSCLC treated with platinum-based chemotherapy and then replicated the results in an independent set of 384 patients, in whom we evaluated associations with overall survival (OS) and progress-free survival (PFS) by Kaplan-Meier analysis and Cox hazards regression analysis.In both discovery and validation sets as well as in the pooled analysis, heterozygotes of CASP7 rs2227310 and rs4353229 as well as rs12415607 variant allele were strongly associated with a better OS of NSCLC (in the pooled sample: adjusted hazard ratio [HR], 0.73; 95% CI = 0.59-0.90; P = .003; HR, 0.72; 95% CI = 0.59-0.89; P = .002; and HR, 0.76; 95% CI = 0.62-0.94; P = .009; respectively). In stratified analyses of the pooled data set, treated with paclitaxel, individuals carrying variant allele of rs2227310, rs4353229, and rs12415607 had significantly improved OS (HR, 0.60; 95% CI = 0.41-0.87; P = .008; HR, 0.58; 95% CI = 0.39-0.84; P = .004; and HR, 0.61; 95% CI = 0.42-0.89; P = .010; respectively).This study provides evidence that genetic variations of CASP7 may modulate OS and PFS of patients with advanced NSCLC treated with platinum-based chemotherapy.

Authors

Qian, J; Gu, S; Wu, Q; Zhao, X; Wu, W; Gao, Z; Zhang, W; Tan, X; Wang, H; Wang, J; Fan, W; Chen, H; Han, B; Lu, D; Wei, Q; Jin, L

MLA Citation

Qian, J, Gu, S, Wu, Q, Zhao, X, Wu, W, Gao, Z, Zhang, W, Tan, X, Wang, H, Wang, J, Fan, W, Chen, H, Han, B, Lu, D, Wei, Q, and Jin, L. "Association of CASP7 polymorphisms and survival of patients with non-small cell lung cancer with platinum-based chemotherapy treatment." Chest 142.3 (September 2012): 680-689.

PMID

22441531

Source

epmc

Published In

Chest

Volume

142

Issue

3

Publish Date

2012

Start Page

680

End Page

689

DOI

10.1378/chest.11-2522

Polymorphic BRCA1 is a vital tumor suppressor gene within the DNA double-strand break repair pathways, but its association with salivary gland carcinoma (SGC) has yet to be investigated.In a case-control study of 156 SGC patients and 511 controls, we used unconditional logistical regression analyses to investigate the association between SGC risk and seven common functional single-nucleotide polymorphisms (A1988G, A31875G, C33420T, A33921G, A34356G, T43893C and A55298G) in BRCA1.T43893C TC/CC genotype was associated with a reduction of SGC risk (adjusted odds ratio=0.55, 95% CI: 0.38-0.80, Bonferroni-adjusted p=0.011), which was more pronounced in women, non-Hispanic whites, and individuals with a family history of cancer in first-degree relatives. The interaction between T43893C and family history of cancer was significant (p=0.009). The GATGGCG and AACAACA haplotypes, both of which carry the T43893C minor allele, were also associated with reduced SGC risk.Our results suggest that polymorphic BRCA1, particularly T43893C polymorphism, may protect against SGC.

Authors

Xu, L; Doan, PC; Wei, Q; Li, G; Sturgis, EM

MLA Citation

Xu, L, Doan, PC, Wei, Q, Li, G, and Sturgis, EM. "Functional single-nucleotide polymorphisms in the BRCA1 gene and risk of salivary gland carcinoma." Oral oncology 48.9 (September 2012): 842-847.

PMID

22503699

Source

epmc

Published In

Oral Oncology

Volume

48

Issue

9

Publish Date

2012

Start Page

842

End Page

847

DOI

10.1016/j.oraloncology.2012.03.012

To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6]. After combining genotypes of seven polymorphisms and using the low-risk group (0-3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium-risk (4 combined risk genotypes) and high-risk groups (5-7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1-2.5) and 1.2 (95% CI, 0.7-1.9) for oral cancer risk, respectively, whereas the low-risk, medium-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2-3.6), 4.0 (95% CI, 1.8-9.1) and 19.1 (95% CI, 5.7-64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53-related genes may modify risk of HPV16-associated oral cancer, especially in young patients, never-smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.

Authors

Wang, Z; Sturgis, EM; Zhang, Y; Huang, Z; Zhou, Q; Wei, Q; Li, G

MLA Citation

Wang, Z, Sturgis, EM, Zhang, Y, Huang, Z, Zhou, Q, Wei, Q, and Li, G. "Combined p53-related genetic variants together with HPV infection increase oral cancer risk." International journal of cancer 131.3 (August 2012): E251-E258.

PMID

22052649

Source

epmc

Published In

International Journal of Cancer

Volume

131

Issue

3

Publish Date

2012

Start Page

E251

End Page

E258

DOI

10.1002/ijc.27335

Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene-environment interactions. To determine gene-asbestos interactions in lung cancer risk, we conducted genome-wide gene-environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10(-6), which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10(-5)). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene-asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk.

Authors

Wei, S; Wang, L-E; McHugh, MK; Han, Y; Xiong, M; Amos, CI; Spitz, MR; Wei, QW

MLA Citation

Wei, S, Wang, L-E, McHugh, MK, Han, Y, Xiong, M, Amos, CI, Spitz, MR, and Wei, QW. "Genome-wide gene-environment interaction analysis for asbestos exposure in lung cancer susceptibility." Carcinogenesis 33.8 (August 2012): 1531-1537.

PMID

22637743

Source

epmc

Published In

Carcinogenesis

Volume

33

Issue

8

Publish Date

2012

Start Page

1531

End Page

1537

DOI

10.1093/carcin/bgs188

Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.Primary data.Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01).These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Authors

Hartz, SM; Short, SE; Saccone, NL; Culverhouse, R; Chen, L; Schwantes-An, T-H; Coon, H; Han, Y; Stephens, SH; Sun, J; Chen, X; Ducci, F; Dueker, N; Franceschini, N; Frank, J; Geller, F; Gubjartsson, D; Hansel, NN; Jiang, C; Keskitalo-Vuokko, K; Liu, Z; Lyytikäinen, L-P; Michel, M; Rawal, R; Rosenberger, A; Scheet, P; Shaffer, JR; Teumer, A; Thompson, JR; Vink, JM; Vogelzangs, N; Wenzlaff, AS; Wheeler, W; Xiao, X; Yang, B-Z; Aggen, SH; Balmforth, AJ; Baumeister, SE; Beaty, T; Bennett, S et al.

MLA Citation

Hartz, SM, Short, SE, Saccone, NL, Culverhouse, R, Chen, L, Schwantes-An, T-H, Coon, H, Han, Y, Stephens, SH, Sun, J, Chen, X, Ducci, F, Dueker, N, Franceschini, N, Frank, J, Geller, F, Gubjartsson, D, Hansel, NN, Jiang, C, Keskitalo-Vuokko, K, Liu, Z, Lyytikäinen, L-P, Michel, M, Rawal, R, Rosenberger, A, Scheet, P, Shaffer, JR, Teumer, A, Thompson, JR, Vink, JM, Vogelzangs, N, Wenzlaff, AS, Wheeler, W, Xiao, X, Yang, B-Z, Aggen, SH, Balmforth, AJ, Baumeister, SE, Beaty, T, and Bennett, S et al. "Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers." Archives of general psychiatry 69.8 (August 2012): 854-860.

PMID

22868939

Source

epmc

Published In

Archives of General Psychiatry

Volume

69

Issue

8

Publish Date

2012

Start Page

854

End Page

860

DOI

10.1001/archgenpsychiatry.2012.124

The unique effects of neighborhood-level economic deprivation on survival, recurrence, and second primary malignancy development were examined using adjusted Cox proportional hazards regression models among 1151 incident squamous cell carcinomas of the head and neck patients. Cancer site was examined as a potential moderator. Main analyses yielded null results; however, interaction analyses indicated poorer overall survival [HR=1.59 (1.00-2.53)] and greater second primary malignancy development [HR=2.99 (1.46-6.11)] among oropharyngeal cancer patients from highly deprived neighborhoods relative to less deprived neighborhoods. Results suggest a dual focus on individual and neighborhood risk factors could help improve clinical outcomes among oropharyngeal cancer patients.

Authors

Reitzel, LR; Nguyen, N; Zafereo, ME; Li, G; Wei, Q; Sturgis, EM

MLA Citation

Reitzel, LR, Nguyen, N, Zafereo, ME, Li, G, Wei, Q, and Sturgis, EM. "Neighborhood deprivation and clinical outcomes among head and neck cancer patients." Health & place 18.4 (July 2012): 861-868.

PMID

22445028

Source

epmc

Published In

Health & Place

Volume

18

Issue

4

Publish Date

2012

Start Page

861

End Page

868

DOI

10.1016/j.healthplace.2012.03.005

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case-control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03-1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01-1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P(trend) = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P(trend) = 0.003) as well as for 261 subjects with different ethnicities (P(trend) = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

Authors

He, J; Qiu, L-X; Wang, M-Y; Hua, R-X; Zhang, R-X; Yu, H-P; Wang, Y-N; Sun, M-H; Zhou, X-Y; Yang, Y-J; Wang, J-C; Jin, L; Wei, Q-Y; Li, J

MLA Citation

He, J, Qiu, L-X, Wang, M-Y, Hua, R-X, Zhang, R-X, Yu, H-P, Wang, Y-N, Sun, M-H, Zhou, X-Y, Yang, Y-J, Wang, J-C, Jin, L, Wei, Q-Y, and Li, J. "Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations." Human genetics 131.7 (July 2012): 1235-1244.

PMID

22371296

Source

epmc

Published In

Human Genetics

Volume

131

Issue

7

Publish Date

2012

Start Page

1235

End Page

1244

DOI

10.1007/s00439-012-1152-8

BACKGROUND: A novel variant rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with risk of esophageal squamous cell carcinoma (ESCC) by 2 large-scale genome-wide association studies (GWASs) in Chinese populations. In this study, we aimed to assess such an association in an eastern Chinese population and to address its possibly functional role in the etiology of ESCC. METHODS: A total of 1061 ESCC cases and 1211 controls were recruited and successfully genotyped for 2 single nucleotide polymorphisms (SNPs) (rs2274223 and rs11187870) of the PLCE1 gene by the TaqMan assay. Real-time PCR and immunohistochemical (IHC) analysis were applied to assess mRNA and protein expression levels, respectively, in a subset of tumor samples. RESULTS: SNP rs2274223 was independently associated with risk of ESCC (adjusted odds ratio [OR], 1.49; 95% confidence interval [95% CI], 1.03-2.17 for GG vs AA), and SNP rs11187870 was also found to be associated with risk of ESCC assuming a dominant model (adjusted OR, 1.20; 95% CI, 1.00-1.44 for CG/CC vs GG). The Grs2274223Crs11187870 haplotype increased the risk for ESCC by 1.22-fold (95% CI, 1.04-1.42). Further experiments showed that overall PLCE1 mRNA expression was lower in tumor than in paired normal tissues (0.067±0.016 vs 0.264±0.067, P<.05), and the IHC analysis showed the normal tissues of rs2274223 GG genotype had a lower PLCE1 staining score than that of the AG genotype (0.40±0.22 vs 1.33±0.32, P<.05). CONCLUSIONS: PLCE1 SNP rs2274223 A>G change may reduce gene expression, and the variant G genotypes might contribute to risk of ESCC.

Authors

Hu, H; Yang, J; Sun, Y; Yang, Y; Qian, J; Jin, L; Wang, M; Bi, R; Zhang, R; Zhu, M; Sun, M; Ma, H; Wei, Q; Jiang, G; Zhou, X; Chen, H

MLA Citation

Hu, H, Yang, J, Sun, Y, Yang, Y, Qian, J, Jin, L, Wang, M, Bi, R, Zhang, R, Zhu, M, Sun, M, Ma, H, Wei, Q, Jiang, G, Zhou, X, and Chen, H. "Putatively functional PLCE1 variants and susceptibility to esophageal squamous cell carcinoma (ESCC): a case-control study in eastern Chinese populations." Annals of surgical oncology 19.7 (July 2012): 2403-2410.

PMID

22203178

Source

epmc

Published In

Annals of Surgical Oncology

Volume

19

Issue

7

Publish Date

2012

Start Page

2403

End Page

2410

DOI

10.1245/s10434-011-2160-y

ATM is critical in response to ionizing radiation-induced DNA damage.Variations in ATM are hypothesized to affect individual susceptibility to thyroid cancer. Our objective was to evaluate the association between ATM polymorphisms and thyroid cancer risk.Six ATM single nucleotide polymorphisms (SNP) were genotyped in two independent case-control series including 592 patients with differentiated thyroid carcinoma (DTC) and 885 healthy individuals. An unconditional logistic regression model was applied to calculate odds ratios (OR) and 95% confidence intervals (CI) for each SNP with respect to risk of DTC and the combination effect of SNP on cancer risk.The risk-allele frequencies of all the SNP were similar in the two case-control populations. Under a dominant model of inheritance, the G allele of ATM rs189037 exhibited a protective effect against DTC (adjusted OR = 0.8; 95% CI, 0.6-1.0; P = 0.04), and the G allele of rs1800057 was associated with increased risk of DTC (adjusted OR = 1.9; 95% CI, 1.1-3.1; P = 0.02). A protective haplotype (A-G-C-T-C-A) was associated with decreased risk of DTC in non-Hispanic whites (adjusted OR = 0.2; 95% CI, 0.0-0.8; P = 0.03). A significant dose-response relationship was observed between the total number of risk alleles of ATM and DTC risk (P = 0.01). Carriers of a combination of six to seven and eight to 10 risk alleles were at 30% (adjusted OR = 1.3; 95% CI, 1.0-1.7) and 50% (adjusted OR = 1.5; 95% CI, 1.1-2.1) increased risk of DTC, respectively.Individual susceptibility to DTC may be attributable to polymorphisms of ATM, and the associations warrant confirmation in independent studies.

Authors

Xu, L; Morari, EC; Wei, Q; Sturgis, EM; Ward, LS

MLA Citation

Xu, L, Morari, EC, Wei, Q, Sturgis, EM, and Ward, LS. "Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma." The Journal of clinical endocrinology and metabolism 97.6 (June 2012): 1913-1921.

PMID

22438227

Source

epmc

Published In

Journal of Clinical Endocrinology and Metabolism

Volume

97

Issue

6

Publish Date

2012

Start Page

1913

End Page

1921

DOI

10.1210/jc.2011-3299

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Authors

Laurie, CC; Laurie, CA; Rice, K; Doheny, KF; Zelnick, LR; McHugh, CP; Ling, H; Hetrick, KN; Pugh, EW; Amos, C; Wei, Q; Wang, L-E; Lee, JE; Barnes, KC; Hansel, NN; Mathias, R; Daley, D; Beaty, TH; Scott, AF; Ruczinski, I; Scharpf, RB; Bierut, LJ; Hartz, SM; Landi, MT; Freedman, ND; Goldin, LR; Ginsburg, D; Li, J; Desch, KC; Strom, SS; Blot, WJ; Signorello, LB; Ingles, SA; Chanock, SJ; Berndt, SI; Le Marchand, L; Henderson, BE; Monroe, KR; Heit, JA; de Andrade, M; Armasu, SM; Regnier, C; Lowe, WL et al.

MLA Citation

Laurie, CC, Laurie, CA, Rice, K, Doheny, KF, Zelnick, LR, McHugh, CP, Ling, H, Hetrick, KN, Pugh, EW, Amos, C, Wei, Q, Wang, L-E, Lee, JE, Barnes, KC, Hansel, NN, Mathias, R, Daley, D, Beaty, TH, Scott, AF, Ruczinski, I, Scharpf, RB, Bierut, LJ, Hartz, SM, Landi, MT, Freedman, ND, Goldin, LR, Ginsburg, D, Li, J, Desch, KC, Strom, SS, Blot, WJ, Signorello, LB, Ingles, SA, Chanock, SJ, Berndt, SI, Le Marchand, L, Henderson, BE, Monroe, KR, Heit, JA, de Andrade, M, Armasu, SM, Regnier, C, and Lowe, WL et al. "Detectable clonal mosaicism from birth to old age and its relationship to cancer." Nature genetics 44.6 (May 6, 2012): 642-650.

PMID

22561516

Source

epmc

Published In

Nature Genetics

Volume

44

Issue

6

Publish Date

2012

Start Page

642

End Page

650

DOI

10.1038/ng.2271

The cooperation between phorbol 12-myristate 13-acetate induced protein 1 (NOXA) and myeloid cell leukemia 1 (MCL1) is critical in the intrinsic apoptotic pathway. Human papillomavirus 16 (HPV16), by inducing p53 and pRb-E2F degradation, may play an essential role in development of squamous cell carcinoma of the head and neck (SCCHN) through NOXA-MCL1 axis-mediated apoptosis. Therefore, genetic variants of NOXA and MCL1 may modify the SCCHN risk associated with HPV16 seropositivity.HPV16 serology was obtained by immunoadsorption assay. Four functional SNPs in the promoter of NOXA (rs9957673, rs4558496) and MCL1 (rs9803935, rs3738485) were genotyped for 380 cases and 335 frequency-matched cancer-free controls of non-Hispanic whites.Associations between the four polymorphisms and SCCHN risk were not significant, while we observed a significantly joint effect on SCCHN risk between the polymorphisms and HPV16 seropositivity. Notably, this effect modification was particularly pronounced for oropharyngeal cancer in subgroups including never smokers, never drinkers and younger subjects.Our results suggested that polymorphisms of NOXA and MCL1 may modify the risk of HPV16-associated oropharyngeal cancer. The further identification of population subgroups at higher risk provides evidence that HPV-targeting treatment may help benefit SCCHN. However, larger studies are needed to validate our findings.

Authors

Zhou, Z; Sturgis, EM; Liu, Z; Wang, L-E; Wei, Q; Li, G

MLA Citation

Zhou, Z, Sturgis, EM, Liu, Z, Wang, L-E, Wei, Q, and Li, G. "Genetic variants of NOXA and MCL1 modify the risk of HPV16-associated squamous cell carcinoma of the head and neck." BMC cancer 12 (May 2012): 159-.

PMID

22548841

Source

epmc

Published In

BMC Cancer

Volume

12

Publish Date

2012

Start Page

159

DOI

10.1186/1471-2407-12-159

The p73 gene (1p36-33) is involved in cancer development through cell growth inhibition by inducing apoptosis in a p53-like manner. The p73 G4C14-to-A4T14 dinucleotide polymorphism, consisting of two single-nucleotide polymorphisms in the non-coding region of exon 2 that are in complete linkage disequilibrium, has been extensively studied in association with cancer risk. We performed a meta-analysis of published studies that examined the association between this p73 G4C14-to-A4T14 polymorphism and cancer by searching for relevant studies on Medline and Embase up to February 28, 2010. Pooling data from 19 case-control studies that included 6510 cancer cases and 5711 controls, we found that carriers of the p73 G4C14-to-A4T14 homozygous variant genotype (AT/AT) had an increased global risk of cancer [odds ratio (OR) = 1.30, 95% confidence interval (CI), 1.03-1.65]. There was no evidence of an effect modification of p73 AT/AT by age, gender, ethnicity or smoking status in subgroup analyses; however, a 1.35-fold statistically significant increased risk was found among individuals <55 years old. In case-only analysis, the homozygous p73 G4C14-to-A4T14 variant of p73 genotype was associated with the presence of the p53 exon 4 Arg72Pro allele (OR = 1.30, 95% CI, 1.02-1.64), which is suggestive of a biological interaction between the two genes in carcinogenesis. In conclusion, the p73 G4C14-to-A4T14 homozygous variant genotype might be a risk factor for cancer, especially in combination with the p53 exon 4 Arg72Pro polymorphism. Further studies looking at p73 G4C14-to-A4T14 and p53 exon 4 Arg72Pro interaction are required to support our findings.

Authors

De Feo, E; Simone, B; Kamgaing, RS; Gallì, P; Hamajima, N; Hu, Z; Li, G; Li, Y; Matsuo, K; Park, JY; Roychoudhury, S; Spitz, MR; Wei, Q; Zhang, J-H; Ricciardi, W; Boccia, S

MLA Citation

De Feo, E, Simone, B, Kamgaing, RS, Gallì, P, Hamajima, N, Hu, Z, Li, G, Li, Y, Matsuo, K, Park, JY, Roychoudhury, S, Spitz, MR, Wei, Q, Zhang, J-H, Ricciardi, W, and Boccia, S. "p73 G4C14-to-A4T14 gene polymorphism and interaction with p53 exon 4 Arg72Pro on cancer susceptibility: a meta-analysis of the literature." Mutagenesis 27.3 (May 2012): 267-273.

PMID

21976716

Source

epmc

Published In

Mutagenesis

Volume

27

Issue

3

Publish Date

2012

Start Page

267

End Page

273

DOI

10.1093/mutage/ger065

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (-460 T > C [rs833061], -634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP ≥grade 3) in 195 NSCLC patients. We found that the VEGF genotypes of rs2010963 and rs3025039 single nucleotide polymorphisms as well as the -460C/-634G/+936C haplotype were predictors of RP development (adjusted hazard ratio [adjHR] = 2.33, 95% confidence interval [CI], 1.01-5.37, P = 0.047 for CC vs GG genotypes; adjHR = 28.13, 95% CI, 5.24-151.02, P < 0.001 for TT vs CC genotypes; and adjHR = 2.51, 95% CI, 1.27-4.98, P = 0.008 for T-C-T vs C-G-C haplotypes). In addition, there was a trend towards reduced RP risk in patients carrying an increased number of protective VEGF genotypes. Our data suggest that VEGF polymorphisms can modulate the risk of radiation pneumonitis in NSCLC patients treated with definitive radiotherapy. Large and independent studies are needed to confirm our findings.

Authors

Yin, M; Liao, Z; Yuan, X; Guan, X; O'Reilly, MS; Welsh, J; Wang, L-E; Wei, Q

MLA Citation

Yin, M, Liao, Z, Yuan, X, Guan, X, O'Reilly, MS, Welsh, J, Wang, L-E, and Wei, Q. "Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy." Cancer science 103.5 (May 2012): 945-950.

PMID

22320189

Source

epmc

Published In

Cancer Science

Volume

103

Issue

5

Publish Date

2012

Start Page

945

End Page

950

DOI

10.1111/j.1349-7006.2012.02229.x

Authors

Wang, L-E; Amos, CI; Spitz, MR; Wei, Q

MLA Citation

Wang, L-E, Amos, CI, Spitz, MR, and Wei, Q. "Reply to K.A. Olaussen et al." Journal of Clinical Oncology 30.13 (May 2012): 1568-1569.

Source

crossref

Published In

Journal of Clinical Oncology

Volume

30

Issue

13

Publish Date

2012

Start Page

1568

End Page

1569

DOI

10.1200/JCO.2011.41.1728

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have been implicated in childhood acute lymphoblastic leukemia (ALL) risk, but previously published studies were inconsistent and recent meta-analyses were not adequate. PROCEDURES: In a meta-analysis of 21 publications with 4,706 cases and 7,414 controls, we used more stringent inclusion method and summarized data on associations between MTHFR C677T and A1298C polymorphisms and childhood ALL risk. RESULTS: We found an overall association between 677T variant genotypes and reduced childhood ALL risk. Specifically, in the dominant genetic model, an association was found in a fixed-effect (TT + CT vs. CC: OR = 0.92; 95% CI = 0.85-0.99) but not random-effect model, whereas such an association was observed in both homozygote genetic model (TT vs. CC: OR = 0.80; 95% CI = 0.70-0.93 by fixed effects and OR = 0.78; 95% CI = 0.65-0.93 by random effects) and recessive genetic model (TT vs. CC + CT: OR = 0.83; 95% CI = 0.72-0.95 by fixed effects and OR = 0.84; 95% CI = 0.73-0.97 by random effects). These associations were also observed in subgroups by ethnicity: for Asians in all models except for the dominant genetic model by random effect and for Caucasians in all models except for the recessive genetic model. However, the A1298C polymorphism did not appear to have an effect on childhood ALL risk. CONCLUSIONS: These results suggest that the MTHFR C677T, but not A1298C, polymorphism is a potential biomarker for childhood ALL risk.

Authors

Yan, J; Yin, M; Dreyer, ZE; Scheurer, ME; Kamdar, K; Wei, Q; Okcu, MF

MLA Citation

Yan, J, Yin, M, Dreyer, ZE, Scheurer, ME, Kamdar, K, Wei, Q, and Okcu, MF. "A meta-analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children." Pediatric blood & cancer 58.4 (April 2012): 513-518. (Review)

PMID

21495160

Source

epmc

Published In

Pediatric Blood & Cancer

Volume

58

Issue

4

Publish Date

2012

Start Page

513

End Page

518

DOI

10.1002/pbc.23137

Authors

Song, F; Qureshi, AA; Zhang, J; Amos, CI; Lee, JE; Wei, Q; Han, J

MLA Citation

Song, F, Qureshi, AA, Zhang, J, Amos, CI, Lee, JE, Wei, Q, and Han, J. "Corrigendum to “Exonuclease 1 (EXO1) gene variation and melanoma risk” 11 (2012) 304–309." DNA Repair 11.4 (April 2012): 449-449.

Source

crossref

Published In

DNA Repair

Volume

11

Issue

4

Publish Date

2012

Start Page

449

End Page

449

DOI

10.1016/j.dnarep.2012.02.002

Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of breast cancer. In this case-control study of 515 young women (≤ 55 years) with newly diagnosed sporadic breast cancer and 402 cancer-free controls, we examined the radiosensitivity as measured by the frequency of chromatid breaks induced by gamma-radiation exposure in the G2 phase of phytohemagglutinin-stimulated and short-term cultured fresh lymphocytes. We found that the average chromatid breaks per cell from 50 well-spread metaphases were statistically significantly higher in 403 non-Hispanic White breast cancer patients (0.52 ± 0.22) than that in 281 non-Hispanic White controls (0.44 ± 0.16) (P value < 0.001), and in 60 Mexican American breast cancer patients (0.52 ± 0.19) than that in 65 Mexican American controls (0.44 ± 0.16) (P value = 0.021), but the difference was not significant in African Americans (52 cases [0.45 ± 0.16] versus 56 controls [0.47 ± 0.16], P = 0.651). The frequency of chromatid breaks per cell above the median of control subjects was associated with two-fold increased risk for breast cancer in non-Hispanic Whites and Mexican Americans. A dose-response relationship was evident between radiosensitivity and risk for breast cancer (P (trend) < 0.001) in these two ethnic groups. We concluded that gamma-ray-induced mutagen sensitivity may play a role in susceptibility to breast cancer in young non-Hispanic White and Mexican American women.

Authors

Wang, L-E; Han, CH; Xiong, P; Bondy, ML; Yu, T-K; Brewster, AM; Shete, S; Arun, BK; Buchholz, TA; Wei, Q

MLA Citation

Wang, L-E, Han, CH, Xiong, P, Bondy, ML, Yu, T-K, Brewster, AM, Shete, S, Arun, BK, Buchholz, TA, and Wei, Q. "Gamma-ray-induced mutagen sensitivity and risk of sporadic breast cancer in young women: a case-control study." Breast cancer research and treatment 132.3 (April 2012): 1147-1155.

PMID

22218884

Source

epmc

Published In

Breast Cancer Research and Treatment

Volume

132

Issue

3

Publish Date

2012

Start Page

1147

End Page

1155

DOI

10.1007/s10549-011-1940-1

Recently, we reported on the associations of seven single nucleotide polymorphisms (SNPs) in the promoter region of MMP1 gene with susceptibility to cutaneous melanoma (CM). Considering the reported correlation between MMP1 expression and melanoma progression, we hypothesized that these promoter SNPs might affect CM progression and prognosis. In this study, we examined the associations of seven SNPs with overall survival, as well as six clinicopathological factors in 754 patients with CM. After adjustment for 11 covariates, we observed significant associations of the SNP -422A>T (rs475007) with ulceration status (P=0.012), primary tumor thickness (P=0.040), and anatomic site (P=0.030). We also observed significant associations of the SNP -755T>G (rs498186) with ulceration status (P=0.038) and anatomic site (P=0.003). Two SNPs, -839G>A and -519A>G, were marginally associated with primary tumor thickness, ulceration status, and anatomic site. Furthermore, the frequency of haplotype 2G-G-G-A-A-G-T was higher in patients with ulceration (odds ratio=2.18, 95% confidence interval: 1.08-4.40, P=0.030) compared with those without ulceration. However, we did not find significant associations of these SNPs with overall survival and other clinical factors. As primary tumor thickness and ulceration status are two important indicators of tumor progression and have significant associations with melanoma prognosis, our results suggested that these promoter SNPs in MMP1 might have potential effects on melanoma progression and prognosis by influencing related clinical factors.

Authors

Liu, H; Wei, Q; Gershenwald, JE; Prieto, VG; Lee, JE; Duvic, M; Grimm, EA; Wang, L-E

MLA Citation

Liu, H, Wei, Q, Gershenwald, JE, Prieto, VG, Lee, JE, Duvic, M, Grimm, EA, and Wang, L-E. "Influence of single nucleotide polymorphisms in the MMP1 promoter region on cutaneous melanoma progression." Melanoma research 22.2 (April 2012): 169-175.

PMID

22198560

Source

epmc

Published In

Melanoma Research

Volume

22

Issue

2

Publish Date

2012

Start Page

169

End Page

175

DOI

10.1097/cmr.0b013e32834fc46b

It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR-16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA-484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers.

Authors

Hu, Z; Dong, J; Wang, L-E; Ma, H; Liu, J; Zhao, Y; Tang, J; Chen, X; Dai, J; Wei, Q; Zhang, C; Shen, H

MLA Citation

Hu, Z, Dong, J, Wang, L-E, Ma, H, Liu, J, Zhao, Y, Tang, J, Chen, X, Dai, J, Wei, Q, Zhang, C, and Shen, H. "Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls." Carcinogenesis 33.4 (April 2012): 828-834.

PMID

22298638

Source

epmc

Published In

Carcinogenesis

Volume

33

Issue

4

Publish Date

2012

Start Page

828

End Page

834

DOI

10.1093/carcin/bgs030

Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (Ptrend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.

Authors

Wang, Z; Sturgis, EM; Zhang, F; Lei, D; Liu, Z; Xu, L; Song, X; Wei, Q; Li, G

MLA Citation

Wang, Z, Sturgis, EM, Zhang, F, Lei, D, Liu, Z, Xu, L, Song, X, Wei, Q, and Li, G. "Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck." Molecular cancer 11 (March 26, 2012): 17-.

PMID

22449259

Source

epmc

Published In

Molecular Cancer

Volume

11

Publish Date

2012

Start Page

17

DOI

10.1186/1476-4598-11-17

The p53 pathway plays a critical role in maintaining genomic stability and preventing tumor formation. Given the roles of both MDM4 and HPV16 E6 oncoproteins in inhibition of p53 activity, we tested the hypothesis that MDM4 polymorphisms are associated with the risk of HPV16-associated squamous cell carcinoma of head and neck (SCCHN).Genotyping was conducted on 3 tagging single nucleotide polymorphisms (rs11801299 G>A, rs10900598 G>T, and rs1380576 C>G) in MDM4, and serology was used to determine HPV 16 exposure in 380 cases and 335 cancer-free controls that were frequency-matched by age, sex, smoking, and drinking status.None of 3 MDM4 polymorphisms alone was significantly associated with risk of overall SCCHN. With further analysis stratified by HPV16 serology and tumor site, we found that each polymorphism individually modified the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly pronounced in never smokers and never drinkers.The risk of HPV16-associated SCCOP could be modified by MDM4 polymorphisms. Large and prospective studies are needed to validate our findings.

Authors

Yu, H; Sturgis, EM; Liu, Z; Wang, L-E; Wei, Q; Li, G

MLA Citation

Yu, H, Sturgis, EM, Liu, Z, Wang, L-E, Wei, Q, and Li, G. "Modifying effect of MDM4 variants on risk of HPV16-associated squamous cell carcinoma of oropharynx." Cancer 118.6 (March 2012): 1684-1692.

PMID

21823114

Source

epmc

Published In

Cancer

Volume

118

Issue

6

Publish Date

2012

Start Page

1684

End Page

1692

DOI

10.1002/cncr.26423

DNA repair pathway genes play an important role in maintaining genomic integrity and protecting against cancer development. This study aimed to identify novel SNPs in the DNA repair-related genes associated with melanoma risk from a genome-wide association study (GWAS).A total of 8422 SNPs from the 165 DNA repair-related genes were extracted from a GWAS of melanoma risk, including 494 cases and 5628 controls from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). We further replicated the top SNPs in a GWAS of melanoma risk from the MD Anderson Cancer Center (1804 cases and 1026 controls).A total of 3 SNPs with P value <0.001 were selected for in silico replication. One SNP was replicated: rs3902093 [A] in EXO1 promoter region (P(discovery)=6.6 × 10⁻⁴, P(replication)=0.039, P(joint)=2.5 × 10⁻⁴; OR(joint)=0.80, 95% CI: 0.71, 0.90). This SNP was associated with the expression of the EXO1; carriers of the A allele showed lower expression (P=0.002).Our study found that a promoter region SNP in the editing and processing nucleases gene EXO1 was associated with decreased expression of EXO1 and decreased melanoma risk. Further studies are warranted to validate this association and to investigate the potential mechanisms.

Authors

Song, F; Qureshi, AA; Zhang, J; Amos, CI; Lee, JE; Wei, Q; Han, J

MLA Citation

Song, F, Qureshi, AA, Zhang, J, Amos, CI, Lee, JE, Wei, Q, and Han, J. "Exonuclease 1 (EXO1) gene variation and melanoma risk." DNA repair 11.3 (March 2012): 304-309.

PMID

22230721

Source

epmc

Published In

DNA Repair

Volume

11

Issue

3

Publish Date

2012

Start Page

304

End Page

309

DOI

10.1016/j.dnarep.2011.12.005

Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since the 1980s. Although the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid carcinoma (DTC). Therefore, the authors explored the association between sporadic DTC and family history of cancer.In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer.The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR, 4.1; 95% CI, 1.7-9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR, 4.6; 95% CI, 1.9-11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR, 7.4; 95% CI, 1.8-30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs 35.5%, P = .01).The study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC.

Authors

Xu, L; Li, G; Wei, Q; El-Naggar, AK; Sturgis, EM

MLA Citation

Xu, L, Li, G, Wei, Q, El-Naggar, AK, and Sturgis, EM. "Family history of cancer and risk of sporadic differentiated thyroid carcinoma." Cancer 118.5 (March 2012): 1228-1235.

PMID

21800288

Source

epmc

Published In

Cancer

Volume

118

Issue

5

Publish Date

2012

Start Page

1228

End Page

1235

DOI

10.1002/cncr.26398

The phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mTOR and Ras/Raf/MEK/ERK pathways have been implicated in endometrial tumorigenesis. In this candidate pathway analysis, we investigated associations between genetic variations in these two pathways and both risk and clinical outcomes of endometrial cancer.We genotyped a total of 48 potentially functional SNPs in 11 key genes (AKT1, AKT2, AKT3, BRAF, FRAP1, KRAS, PDPK1, PIK3CA, PIK3CB, PIK3R1, and PTEN) with the Sequenom genotyping platform in 115 endometrial cancer patients and 230 cancer-free women to evaluate their associations with risk, survival, and recurrence of endometrial cancer.We found the following: (1) PIK3CA rs6443624 and rs9838411 variants either borderline or significantly decreased risk of endometrial cancer in a dominant model (adjusted odds ratio [OR], 0.62; 95% CI, 0.39-1.00 and 0.59; 95% CI, 0.36-0.95, respectively). Furthermore, there was a statistically significant multiplicative interaction (P (int) = 0.036) between these two loci in risk of endometrial cancer. In contrast, the AKT1 rs2498801 genotype significantly increased risk of endometrial cancer (adjusted OR, 1.94; 95% CI, 1.02-3.67 in a recessive model). (2) In Cox regression analyses, three SNPs (PIK3R1 rs1862162, AKT2 rs892119, and PIK3CA rs2699887) showed significant associations with survival of endometrial cancer patients. (3) KRAS rs7312175 and PIK3CA rs6443624 had significant effects on recurrence of endometrial cancer individually and combined in a locus-dosage manner (adjusted P (trend) = 0.003).These results suggest that common genetic variations in these pathways may modulate risk and clinical outcomes of endometrial cancer. Further replication and functional studies are needed to confirm these findings.

Authors

Wang, L-E; Ma, H; Hale, KS; Yin, M; Meyer, LA; Liu, H; Li, J; Lu, KH; Hennessy, BT; Li, X; Spitz, MR; Wei, Q; Mills, GB

MLA Citation

Wang, L-E, Ma, H, Hale, KS, Yin, M, Meyer, LA, Liu, H, Li, J, Lu, KH, Hennessy, BT, Li, X, Spitz, MR, Wei, Q, and Mills, GB. "Roles of genetic variants in the PI3K and RAS/RAF pathways in susceptibility to endometrial cancer and clinical outcomes." Journal of cancer research and clinical oncology 138.3 (March 2012): 377-385.

PMID

22146979

Source

epmc

Published In

Journal of Cancer Research and Clinical Oncology

Volume

138

Issue

3

Publish Date

2012

Start Page

377

End Page

385

DOI

10.1007/s00432-011-1103-0

The functional polymorphism (rs1800566) in the NQO1 gene, a 609C>T substitution, leading to proline-to-serine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results.We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C>T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95% CI = 1.01 - 1.19, P(heterogeneity) = 0.27, I(2) = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 - 1.20, P(heterogeneity) = 0.14; I(2) = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies.This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyses suggest that further larger studies are needed, especially for non-colorectal GI cancers in Caucasians and GI cancers in Asians.

Authors

Yu, H; Liu, H; Wang, L-E; Wei, Q

MLA Citation

Yu, H, Liu, H, Wang, L-E, and Wei, Q. "A functional NQO1 609C>T polymorphism and risk of gastrointestinal cancers: a meta-analysis." PloS one 7.1 (January 17, 2012): e30566-.

PMID

22272361

Source

epmc

Published In

PloS one

Volume

7

Issue

1

Publish Date

2012

Start Page

e30566

DOI

10.1371/journal.pone.0030566

Excision repair cross-complementation group 4 gene (ERCC4/XPF) plays an important role in nucleotide excision repair and participates in removal of DNA interstrand cross-links and DNA double-strand breaks. Single nucleotide polymorphisms (SNPs) in ERCC4 may impact repair capacity and affect cancer susceptibility.In this case-control study, we evaluated associations of four selected potentially functional SNPs in ERCC4 with risk of squamous cell carcinoma of the head and neck (SCCHN) in 1,040 non-Hispanic white patients with SCCHN and 1,046 cancer-free matched controls. We found that the variant GG genotype of rs2276466 was significantly associated with a decreased risk of SCCHN (OR = 0.69, 95% CI 0.50-0.96), and that the variant TT genotype of rs3136038 showed a borderline significant decreased risk with SCCHN (OR = 0.76, 95% CI: 0.58-1.01) in the recessive model. Such protective effects were more evident in oropharyngeal cancer (OR = 0.61, 95% CI: 0.40-0.92 for rs2276466; OR = 0.69, 95% CI: 0.48-0.98 for rs3136038). No significant associations were found for the other two SNPs (rs1800067 and rs1799798). In addition, individuals with the rs2276466 GG or with the rs3136038 TT genotypes had higher levels of ERCC4 mRNA expression than those with the corresponding wild-type genotypes in 90 Epstein-Barr virus-transformed lymphoblastoid cell lines derived from Caucasians.These results suggest that these two SNPs (rs2276466 and rs3136038) in ERCC4 may be functional and contribute to SCCHN susceptibility. However, our findings need to be replicated in further large epidemiological and functional studies.

Authors

Yu, H; Liu, Z; Huang, Y-J; Yin, M; Wang, L-E; Wei, Q

MLA Citation

Yu, H, Liu, Z, Huang, Y-J, Yin, M, Wang, L-E, and Wei, Q. "Association between single nucleotide polymorphisms in ERCC4 and risk of squamous cell carcinoma of the head and neck." PloS one 7.7 (January 2012): e41853-.

PMID

22848636

Source

epmc

Published In

PloS one

Volume

7

Issue

7

Publish Date

2012

Start Page

e41853

DOI

10.1371/journal.pone.0041853

In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual's DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu) exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P(trend) = 0.030). Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36-0.98 and adjusted OR = 0.47, 95% CI: 0.26-0.86, respectively; P(trend) = 0.012) among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512). Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression.

Authors

Yu, H; Zhao, H; Wang, L-E; Liu, Z; Li, D; Wei, Q

MLA Citation

Yu, H, Zhao, H, Wang, L-E, Liu, Z, Li, D, and Wei, Q. "Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes." PloS one 7.7 (January 2012): e40131-.

PMID

22792228

Source

epmc

Published In

PloS one

Volume

7

Issue

7

Publish Date

2012

Start Page

e40131

DOI

10.1371/journal.pone.0040131

Nonhomologous end joining (NHEJ) is a pathway that repairs DNA double-strand breaks (DSBs) to maintain genomic stability in response to irradiation. The authors hypothesized that single nucleotide polymorphisms (SNPs) in NHEJ repair genes may affect clinical outcomes in patients with nonsmall cell lung cancer (NSCLC) who receive definitive radio(chemo)therapy.The authors genotyped 5 potentially functional SNPs-x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) reference SNP (rs) number rs6869366 (-1394 guanine to thymine [-1394G→T] change) and rs28360071 (intron 3, deletion/insertion), XRCC5 rs3835 (guanine to adenine [G→A] change at nucleotide 2408), XRCC6 rs2267437 (-1310 cytosine to guanine [C→G) change], and DNA ligase IV (LIG4) rs1805388 (threonine-to-isoleucine change at codon 9 [T9I])-and estimated their associations with severe radiation pneumonitis (RP) (grade ≥3) in 195 patients with NSCLC.A predictive role in radiation pneumonitis (RP) development was observed for the LIG4 SNP rs1805388 (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.12; P = .037 for the CT/TT genotype vs the CC genotype). In addition, men with the TT genotype of the XRCC4 rs6869366 SNP and women with AG + AA genotypes of the XRCC5 rs3835 SNP also were at increased risk of developing severe RP.The current results indicated that NHEJ genetic polymorphisms, particularly LIG4 rs1805388, may modulate the risk of RP in patients with NSCLC who receive definitive radio(chemo)therapy. Large studies will be needed to confirm these findings.

Authors

Yin, M; Liao, Z; Liu, Z; Wang, L-E; O'Reilly, M; Gomez, D; Li, M; Komaki, R; Wei, Q

MLA Citation

Yin, M, Liao, Z, Liu, Z, Wang, L-E, O'Reilly, M, Gomez, D, Li, M, Komaki, R, and Wei, Q. "Genetic variants of the nonhomologous end joining gene LIG4 and severe radiation pneumonitis in nonsmall cell lung cancer patients treated with definitive radiotherapy." Cancer 118.2 (January 2012): 528-535.

PMID

21717429

Source

epmc

Published In

Cancer

Volume

118

Issue

2

Publish Date

2012

Start Page

528

End Page

535

DOI

10.1002/cncr.26214

Xeroderma pigmentosum group G (XPG) protein is essential for the nucleotide excision repair system, and genetic variations in XPG/ERCC5 that affect DNA repair capacity may contribute to the risk of tobacco-induced cancers, including squamous cell carcinoma of the head and neck (SCCHN). We investigated the association between XPG/ERCC5 polymorphisms and risk of SCCHN.We genotyped 12 tagging and potentially functional single nucleotide polymorphisms (SNPs) of XPG/ERCC5 in a case-control study of 1059 non-Hispanic white patients with SCCHN and 1066 cancer-free age- and sex-matched controls, and evaluated their associations with the risk of SCCHN.Multivariate logistic regression showed that only an intronic tagging SNP (rs4150351A/C) of XPG/ERCC5 was associated with a decreased risk of SCCHN (adjusted odds ratio=0.76, 95% confidence interval=0.62-0.92 for AC vs. AA; adjusted odds ratio=0.81, 95% confidence interval=0.67-0.98 for AC/CC vs. AA), but this association was nonsignificant after corrections by the permutation test (empirical P=0.105). In the genotype-phenotype correlation analysis using peripheral lymphocytes from 44 patients with SCCHN, we found that rs4150351 AC/CC was associated with a statistically significant increase in the XPG/ERCC5 mRNA expression.These findings suggest that genetic variation in XPG/ERCC5 may not affect the risk of SCCHN, although rs4150351 C variant genotypes were associated with an increased expression of XPG/ERCC5 mRNA and nonsignificantly decreased risk of SCCHN. Larger population-based and additional functional studies are warranted to validate our findings.

Authors

Ma, H; Yu, H; Liu, Z; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Ma, H, Yu, H, Liu, Z, Wang, L-E, Sturgis, EM, and Wei, Q. "Polymorphisms of XPG/ERCC5 and risk of squamous cell carcinoma of the head and neck." Pharmacogenetics and genomics 22.1 (January 2012): 50-57.

PMID

22108238

Source

epmc

Published In

Pharmacogenetics and Genomics

Volume

22

Issue

1

Publish Date

2012

Start Page

50

End Page

57

DOI

10.1097/fpc.0b013e32834e3cf6

Caspase-8 and caspase-10 play crucial roles in both cancer development and chemotherapy efficacy. In this study, we aimed to comprehensively assess single nucleotide polymorphisms (SNPs) of the caspase-8 (CASP8) and caspase-10 (CASP10) genes in relation to toxicity outcomes with first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 13 tag SNPs of CASP8 and CASP10 in 663 patients with advanced NSCLC treated with platinum-based chemotherapy regimens. Associations between SNPs and chemotherapy toxicity outcomes were identified in a discovery set of 279 patients and then validated in an independent set of 384 patients. In both the discovery and validation sets, variant homozygotes of CASP8 rs12990906 and heterozygotes of CASP8 rs3769827 and CASP10 rs11674246 and rs3731714 had a significantly lower risk for severe toxicity overall. However, only the association with the rs12990906 variant was replicated in the validation set for hematological toxicity risk. In a stratified analysis, we found that some other SNPs, including rs3769821, rs3769825, rs7608692, and rs12613347, were significantly associated with severe toxicity risk in some subgroups, such as in nonsmoking patients, patients with adenocarcinoma, and patients treated with cisplatin combinations. Consistent results were also found in haplotype analyses. Our results provide novel evidence that polymorphisms in CASP8 and CASP10 may modulate toxicity outcomes in patients with advanced NSCLC treated with platinum-based chemotherapy. If validated, the findings will facilitate the genotype-based selection of platinum-based chemotherapy regimens.

Authors

Qian, J; Qu, H-Q; Yang, L; Yin, M; Wang, Q; Gu, S; Wu, Q; Zhao, X; Wu, W; Wu, J; Tan, X; Chen, W; Wang, H; Wang, J; Fan, W; Chen, H; Han, B; Lu, D; Wei, Q; Jin, L

MLA Citation

Qian, J, Qu, H-Q, Yang, L, Yin, M, Wang, Q, Gu, S, Wu, Q, Zhao, X, Wu, W, Wu, J, Tan, X, Chen, W, Wang, H, Wang, J, Fan, W, Chen, H, Han, B, Lu, D, Wei, Q, and Jin, L. "Association between CASP8 and CASP10 polymorphisms and toxicity outcomes with platinum-based chemotherapy in Chinese patients with non-small cell lung cancer." The oncologist 17.12 (January 2012): 1551-1561.

PMID

22843554

Source

epmc

Published In

The oncologist

Volume

17

Issue

12

Publish Date

2012

Start Page

1551

End Page

1561

DOI

10.1634/theoncologist.2011-0419

Poly(ADP-ribose) polymerase-1 (PARP-1 catalyzes poly(ADP-ribosyl)ation to various proteins involved in many cellular processes, including DNA damage detection and repair and cell proliferation and death. PARP-1 has been implicated in human carcinogenesis, but the association between the most-studied PARP-1 V762A polymorphism (rs1136410) and risk of various cancers was reported with inconclusive results. The aim of this study was to assess the association between the PARP-1 V762A polymorphism and cancer risk. A meta-analysis of 21 studies with 12,027 cancer patients and 14,106 cancer-free controls was conducted to evaluate the strength of the association using odds ratio (OR) with 95% confidence interval (CI). Overall, no significant association was found between the PARP-1 V762A polymorphism and cancer risk. In the stratified analyses, however, it was found that the variant A allele of the PARP-1 V762A polymorphism was associated with an increased risk of cancer among Asian populations (VA + AA vs. VV: OR = 1.11, 95% CI: 1.01-1.23; P(heterogeneity) = 0.210), but a decreased risk of cancer (VA + AA vs. VV: OR = 0.89, 95% CI: 0.80-1.00; P(heterogeneity) = 0.004) among Caucasian populations, especially for glioma risk (OR = 0.79, 95% CI: 0.69-0.90; P(heterogeneity) = 0.800). This meta-analysis found evidence for an association of the PARP-1 V 762A polymorphism with increased risk of cancer among Asians, but decreased risk of cancer among Caucasians, particularly of glioma. Further well-designed studies with large sample sizes of different ethnic populations and different cancer types are warranted to confirm these findings.

Authors

Yu, H; Ma, H; Yin, M; Wei, Q

MLA Citation

Yu, H, Ma, H, Yin, M, and Wei, Q. "Association between PARP-1 V762A polymorphism and cancer susceptibility: a meta-analysis." Genetic epidemiology 36.1 (January 2012): 56-65.

PMID

22127734

Source

epmc

Published In

Genetic Epidemiology

Volume

36

Issue

1

Publish Date

2012

Start Page

56

End Page

65

DOI

10.1002/gepi.20663

BACKGROUND: Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. A series of epidemiological studies have examined associations between XPF polymorphisms and cancer risk, but the findings remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: In this meta-analysis of 47,639 cancer cases and 51,915 controls, by searching three electronic databases (i.e., MEDLINE, EMBASE and CNKI), we summarized 43 case-control studies from 29 publications on four commonly studied polymorphisms of XPF (i.e., rs1800067, rs1799801, rs2020955 and rs744154), and we did not find statistical evidence of any significant association with overall cancer risk. However, in stratification analyses, we found a significant association of XPF-rs1799801 with a reduced cancer risk in Caucasian populations (4,845 cases and 5,556 controls; recessive model: OR=0.87, 95% CI=0.76-1.00, P=0.049, P=0.723 for heterogeneity test, I(2) =0). Further genotype-phenotype correlation analysis showed that the homozygous variant CC genotype carriers had higher XPF expression levels than that of the TT genotype carriers (Student's t test for a recessive model: P=0.046). No publication bias was found by using the funnel plot and Egger's test. CONCLUSION: This meta-analysis suggests a lack of statistical evidence for the association between the four XPF SNPs and overall risk of cancers. However, XPF-rs1799801 may be associated with cancer risk in Caucasian populations, which needs to be further validated in single large, well-designed prospective studies.

Authors

Shi, T-Y; He, J; Qiu, L-X; Zhu, M-L; Wang, M-Y; Zhou, X-Y; Han, J; Yu, H; Zang, R-Y; Wei, Q

MLA Citation

Shi, T-Y, He, J, Qiu, L-X, Zhu, M-L, Wang, M-Y, Zhou, X-Y, Han, J, Yu, H, Zang, R-Y, and Wei, Q. "Association between XPF polymorphisms and cancer risk: a meta-analysis." PloS one 7.7 (January 2012): e38606-. (Review)

PMID

22768293

Source

epmc

Published In

PloS one

Volume

7

Issue

7

Publish Date

2012

Start Page

e38606

DOI

10.1371/journal.pone.0038606

BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C) and cancer susceptibility generated conflicting results. METHODOLOGY/PRINCIPAL FINDINGS: To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR = 0.99, 95% CI: 0.92-1.06, P = 0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR = 0.98, 95% CI: 0.93-1.03, P = 0.260 for heterogeneity), nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk.

Authors

Zhu, M-L; Wang, M; Cao, Z-G; He, J; Shi, T-Y; Xia, K-Q; Qiu, L-X; Wei, Q-Y

MLA Citation

Zhu, M-L, Wang, M, Cao, Z-G, He, J, Shi, T-Y, Xia, K-Q, Qiu, L-X, and Wei, Q-Y. "Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis." PloS one 7.7 (January 2012): e36293-.

PMID

22815677

Source

epmc

Published In

PloS one

Volume

7

Issue

7

Publish Date

2012

Start Page

e36293

DOI

10.1371/journal.pone.0036293

Breast cancer 1, early onset (BRCA1) is a vital DNA repair gene, and the single nucleotide polymorphisms (SNPs) of this gene have been studied in diverse cancer types. In this study, we investigated the association between eight common BRCA1 functional SNPs and the risk of differentiated thyroid carcinoma (DTC).This cancer center-based case-control study included 303 DTC cases and 511 controls. A polymerase chain reaction-based restriction fragment length polymorphism assay was performed for genotyping. Unconditional logistical regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in single-SNP analysis and haplotype analysis.A decreased risk of DTC was found for the A1988G heterozygous AG genotype (adjusted OR=0.63, 95% CI: 0.45-0.87, Bonferroni-adjusted p-value=0.036). AATAATA and ATAA haplotypes that carry C33420T variant allele were associated with reduced papillary thyroid cancer risk (adjusted OR=0.52, 95% CI: 0.33-0.84; adjusted OR=0.62, 95% CI: 0.40-0.95, respectively). Also, having a combination of ≥3 favorable genotypes was associated with a DTC risk reduction (adjusted OR=0.69, 95% CI: 0.50-0.95). The A31875G AG/GG genotype was associated with a 69% reduced risk of multifocal primary tumor in DTC patients (adjusted OR=0.31, 95% CI: 0.12-0.81).BRCA1 genetic polymorphisms may play a role in DTC risk, while the possible associations warrant confirmation in independent studies.

Authors

Xu, L; Doan, PC; Wei, Q; Liu, Y; Li, G; Sturgis, EM

MLA Citation

Xu, L, Doan, PC, Wei, Q, Liu, Y, Li, G, and Sturgis, EM. "Association of BRCA1 functional single nucleotide polymorphisms with risk of differentiated thyroid carcinoma." Thyroid : official journal of the American Thyroid Association 22.1 (January 2012): 35-43.

PMID

22136207

Source

epmc

Published In

Thyroid

Volume

22

Issue

1

Publish Date

2012

Start Page

35

End Page

43

DOI

10.1089/thy.2011.0117

p53 and p73 interact with human papillomavirus (HPV) E6 and E7 oncoproteins. The interplay between p53 and p73 and HPV16 may lead to deregulation of cell cycle and apoptosis, through which inflammation/immune responses control the HPV clearance and escape of immune surveillance, and subsequently contribute to tumor HPV16 status. In this case-case comparison study, HPV16 status in tumor specimens was analyzed and p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms were genotyped using genomic DNA from blood of 309 oropharyngeal cancer patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in univariate and multivariable logistic regression models to examine the association. The results from this study showed both p53 variant genotypes (Arg/Pro+Pro/Pro) and p73 variant genotypes (GC/AT+AT/AT) were significantly associated with HPV16-positive tumor in oropharyngeal cancer patients (OR, 1.9, 95% CI, 1.1-3.3 and OR, 2.1, 95% CI, 1.2-3.8, respectively), while the combined variant genotypes (p53 Pro carriers and p73 AT carriers) exhibited a significantly greater association with HPV16-positive tumor (OR, 3.2, 95% CI, 1.4-7.4), compared with combined wild-type genotypes (p53 Arg/Arg and p73 GC/GC), and the association was in a statistically significant dose-effect relationship (p = 0.001). Moreover, such association was more pronounced among several subgroups. These findings suggest that variant genotypes of p53 and p73 genes may be individually, or more likely jointly, associated with tumor HPV16-positive oropharyngeal cancer patients, particularly in never smokers. Identification of such susceptible biomarkers would greatly influence on individualized treatment for an improved prognosis.

Authors

Wang, Z; Sturgis, EM; Guo, W; Song, X; Zhang, F; Xu, L; Wei, Q; Li, G

MLA Citation

Wang, Z, Sturgis, EM, Guo, W, Song, X, Zhang, F, Xu, L, Wei, Q, and Li, G. "Association of combined p73 and p53 genetic variants with tumor HPV16-positive oropharyngeal cancer." PloS one 7.4 (January 2012): e35522-.

PMID

22523600

Source

epmc

Published In

PloS one

Volume

7

Issue

4

Publish Date

2012

Start Page

e35522

DOI

10.1371/journal.pone.0035522

PURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether XPD polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC survival (log-rank P = 0.001). This effect was more predominant for patients with stage IIIB disease (P = 2.21×10(-4), log-rank test). Increased risks for variant haplotypes of XPD were also observed among patients with performance status of 0-1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS: Our study provides evidence for the predictive role of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.

Authors

Wu, W; Li, H; Wang, H; Zhao, X; Gao, Z; Qiao, R; Zhang, W; Qian, J; Wang, J; Chen, H; Wei, Q; Han, B; Lu, D

MLA Citation

Wu, W, Li, H, Wang, H, Zhao, X, Gao, Z, Qiao, R, Zhang, W, Qian, J, Wang, J, Chen, H, Wei, Q, Han, B, and Lu, D. "Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients." PloS one 7.3 (January 2012): e33200-.

PMID

22479369

Source

epmc

Published In

PloS one

Volume

7

Issue

3

Publish Date

2012

Start Page

e33200

DOI

10.1371/journal.pone.0033200

Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14-1.54) and lung cancer (OR = 1.57; 95% CI = 1.31-1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13-1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.

Authors

Yang, L; Qiu, F; Lu, X; Huang, D; Ma, G; Guo, Y; Hu, M; Zhou, Y; Pan, M; Tan, Y; Zhong, H; Ji, W; Wei, Q; Ran, P; Zhong, N; Zhou, Y; Lu, J

MLA Citation

Yang, L, Qiu, F, Lu, X, Huang, D, Ma, G, Guo, Y, Hu, M, Zhou, Y, Pan, M, Tan, Y, Zhong, H, Ji, W, Wei, Q, Ran, P, Zhong, N, Zhou, Y, and Lu, J. "Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese." PloS one 7.10 (January 2012): e46071-.

PMID

23056235

Source

epmc

Published In

PloS one

Volume

7

Issue

10

Publish Date

2012

Start Page

e46071

DOI

10.1371/journal.pone.0046071

Because of the structural and biochemical similarities between the antitumor p53 and p73 proteins, the authors hypothesized that individuals who carry high-risk genotypes of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms have a higher risk of developing second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN).A cohort of 1269 patients with index cases of SCCHN was recruited between May 1995 and January 2007 at The University of Texas MD Anderson Cancer Center and followed for SPM development. Patients were genotyped for p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms. A log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk among different risk groups with the combined risk genotypes of the 2 polymorphisms.The data demonstrated that patients with p53 WP + PP and p73 GC/GC genotypes had a worse SPM-free survival and an increased SPM risk compared with the corresponding p53 WW and p73 GC/AT + AT/AT genotypes. After combining the 2 polymorphisms, a borderline significantly or significantly reduced SPM-free survival and increased SPM risk were observed in the medium-risk group (p53 WW and p73 GC/GC or p53 P carriers and p73 AT carriers) and high-risk group (p53 P carriers and p73 GC/GC) compared with low-risk group (p53 WW and p73 AT carriers), respectively.The results suggest an increased risk of SPM after index SCCHN with both p53 and p73 polymorphisms individually and in combination.

Authors

Zhang, Y; Sturgis, EM; Huang, Z; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Zhang, Y, Sturgis, EM, Huang, Z, Zafereo, ME, Wei, Q, and Li, G. "Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck." Cancer 118.2 (January 2012): 485-492.

PMID

21717430

Source

epmc

Published In

Cancer

Volume

118

Issue

2

Publish Date

2012

Start Page

485

End Page

492

DOI

10.1002/cncr.26222

The p14(ARF)/MDM2/p53 pathway plays an important role in modulation of DNA damage and oxidative stress responses. The aim of this study was to determine whether genetic variants in MDM2 and p14(ARF) are associated with risk of salivary gland carcinoma (SGC).Four single nucleotide polymorphisms (SNPs) in MDM2 and p14(ARF) (MDM2-rs2279744, MDM2-rs937283, p14(ARF)-rs3731217, and p14(ARF)-rs3088440) were genotyped in 156 patients with SGC and 511 cancer-free controls. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs).MDM2-rs2279744 was significantly associated with a moderately increased risk of SGC (OR, 1.5, 95% CI, 1.1-2.2). There was a trend toward significantly increased SGC risk with increasing number of risk genotypes of the four polymorphisms (P(trend) = 0.004). Individuals carrying 3-4 risk genotypes in MDM2 and p14(ARF) were at increased SGC risk (OR, 2.0, 95% CI, 1.1-2.7) compared with individuals carrying 0-2 risk genotypes. Moreover, the combined effect of risk genotypes of MDM2 and p14(ARF) was more pronounced among young subjects (≤ 45 years), female subjects, subjects with race/ethnicity other than non-Hispanic white, ever-smokers, and ever-drinkers.Our results support the involvement of SNPs of MDM2 and p14(ARF), either alone or more likely in combination, in susceptibility to SGC. Larger studies are needed to validate our findings.

Authors

Jin, L; Xu, L; Song, X; Wei, Q; Sturgis, EM; Li, G

MLA Citation

Jin, L, Xu, L, Song, X, Wei, Q, Sturgis, EM, and Li, G. "Genetic variation in MDM2 and p14ARF and susceptibility to salivary gland carcinoma." PloS one 7.11 (January 2012): e49361-.

PMID

23145162

Source

epmc

Published In

PloS one

Volume

7

Issue

11

Publish Date

2012

Start Page

e49361

DOI

10.1371/journal.pone.0049361

Recent data showed that melanoma was more common among patients with Parkinson disease than individuals without Parkinson disease and vice versa. It has been hypothesized that these two diseases may share common genetic and environmental risk factors.We evaluated the association between single-nucleotide polymorphisms (SNP) selected on the basis of recent genome-wide association studies (GWAS) on Parkinson disease risk and the risk of melanoma using 2,297 melanoma cases and 6,651 controls.The Parkinson disease SNP rs156429 in the chromosome 7p15 region was nominally associated with melanoma risk with P value of 0.04, which was not significant after the Bonferroni correction for multiple comparisons. No association was observed between the remaining 31 Parkinson disease SNPs and the risk of melanoma. The genetic score based on the number of Parkinson disease risk allele was not associated with melanoma risk [OR for the highest genetic score quartile (30-35) vs. the lowest (15-20), 1.13, 95% confidence interval (CI), 0.47-2.70].The Parkinson disease SNPs identified in published GWAS do not seem to play an important role in melanoma development.The Parkinson disease susceptibility loci discovered by GWAS contribute little to the observed epidemiologic association between the Parkinson disease and melanoma.

Authors

Meng, S; Song, F; Chen, H; Gao, X; Amos, CI; Lee, JE; Wei, Q; Qureshi, AA; Han, J

MLA Citation

Meng, S, Song, F, Chen, H, Gao, X, Amos, CI, Lee, JE, Wei, Q, Qureshi, AA, and Han, J. "No association between Parkinson disease alleles and the risk of melanoma." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 21.1 (January 2012): 243-245.

PMID

22086882

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

21

Issue

1

Publish Date

2012

Start Page

243

End Page

245

DOI

10.1158/1055-9965.epi-11-0905

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.

Authors

Bodelon, C; Pfeiffer, RM; Bollati, V; Debbache, J; Calista, D; Ghiorzo, P; Fargnoli, MC; Bianchi-Scarra, G; Peris, K; Hoxha, M; Hutchinson, A; Burdette, L; Burke, L; Fang, S; Tucker, MA; Goldstein, AM; Lee, JE; Wei, Q; Savage, SA; Yang, XR; Amos, C; Landi, MT

MLA Citation

Bodelon, C, Pfeiffer, RM, Bollati, V, Debbache, J, Calista, D, Ghiorzo, P, Fargnoli, MC, Bianchi-Scarra, G, Peris, K, Hoxha, M, Hutchinson, A, Burdette, L, Burke, L, Fang, S, Tucker, MA, Goldstein, AM, Lee, JE, Wei, Q, Savage, SA, Yang, XR, Amos, C, and Landi, MT. "On the interplay of telomeres, nevi and the risk of melanoma." PloS one 7.12 (January 2012): e52466-.

PMID

23300679

Source

epmc

Published In

PloS one

Volume

7

Issue

12

Publish Date

2012

Start Page

e52466

DOI

10.1371/journal.pone.0052466

BACKGROUND: Inherited functional single nucleotide polymorphisms (SNPs) in DNA repair genes may alter DNA repair capacity and thus contribute to cancer risk. METHODS: Three ERCC1 functional SNPs (rs2298881C>A, rs3212986C>A and rs11615G>A) and two XPF/ERCC4 functional SNPs (rs2276466C>G and rs6498486A>C) were genotyped for 1125 gastric adenocarcinoma cases and 1196 cancer-free controls by Taqman assays. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate risk associations, and false-positive report probabilities (FPRP) were calculated for assessing significant findings. RESULTS: ERCC1 rs2298881C and rs11615A variant genotypes were associated with increased gastric cancer risk (adjusted OR=1.33, 95% CI=1.05-1.67 for rs2298881 AC/CC and adjusted OR=1.23, 95% CI=1.05-1.46 for rs11615 AG/AA, compared with their common genotype AA and GG, respectively). Patients with 2-3 ERCC1 risk genotypes had significant increased risk (adjusted OR=1.56, 95% CI=1.27-1.93), compared with those with 0-1 ERCC1 risk genotypes, and this risk was more significantly in subgroups of never drinkers, non-gastric cardia adenocarcinoma (NGCA) and clinical stage I+II. All these risks were not observed for XPF SNPs. CONCLUSIONS: These findings suggest that functional ERCC1 SNPs may contribute to risk of gastric cancer. Larger and well-designed studies with different ethnic populations are needed to validate our findings.

Authors

He, J; Xu, Y; Qiu, L-X; Li, J; Zhou, X-Y; Sun, M-H; Wang, J-C; Yang, Y-J; Jin, L; Wei, Q-Y; Wang, Y

MLA Citation

He, J, Xu, Y, Qiu, L-X, Li, J, Zhou, X-Y, Sun, M-H, Wang, J-C, Yang, Y-J, Jin, L, Wei, Q-Y, and Wang, Y. "Polymorphisms in ERCC1 and XPF genes and risk of gastric cancer in an eastern Chinese population." PloS one 7.11 (January 2012): e49308-.

PMID

23166636

Source

epmc

Published In

PloS one

Volume

7

Issue

11

Publish Date

2012

Start Page

e49308

DOI

10.1371/journal.pone.0049308

BACKGROUND: Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair; its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contribute to cancer risk. METHODOLOGY/PRINCIPAL FINDINGS: In a hospital-based case-control study of 1115 esophageal squamous cell carcinoma (ESCC) cases and 1117 cancer-free controls, we genotyped three potentially functional SNPs of ERCC5 (SNPs, rs2296147T>C, rs2094258C>T and rs873601G>A) and estimated crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for their associations with risk of ESCC using unconditional logistic regression models. We also calculated false-positive report probabilities (FPRPs) for significant findings. We found that compared with the TT genotype, ERCC5 rs2296147 C variant genotypes were associated with a significantly lower ESCC risk (CT: adjusted OR = 0.76, 95% CI = 0.63-0.93, CT/CC: adjusted OR = 0.80, 95% CI = 0.67-0.96); however, this risk was not observed for the other two SNPs (rs2094258C>T and rs873601 G>A), nor in further stratification and haplotype analysis. CONCLUSIONS/SIGNIFICANCES: These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations, but the effect was weak and needs further validation by larger population-based case-control studies.

Authors

Zhu, M-L; Shi, T-Y; Hu, H-C; He, J; Wang, M; Jin, L; Yang, Y-J; Wang, J-C; Sun, M-H; Chen, H; Zhao, K-L; Zhang, Z; Chen, H-Q; Xiang, J-Q; Wei, Q-Y

MLA Citation

Zhu, M-L, Shi, T-Y, Hu, H-C, He, J, Wang, M, Jin, L, Yang, Y-J, Wang, J-C, Sun, M-H, Chen, H, Zhao, K-L, Zhang, Z, Chen, H-Q, Xiang, J-Q, and Wei, Q-Y. "Polymorphisms in the ERCC5 gene and risk of esophageal squamous cell carcinoma (ESCC) in Eastern Chinese populations." PloS one 7.7 (January 2012): e41500-.

PMID

22848513

Source

epmc

Published In

PloS one

Volume

7

Issue

7

Publish Date

2012

Start Page

e41500

DOI

10.1371/journal.pone.0041500

BACKGROUND: Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P(trend) = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05). CONCLUSIONS/SIGNIFICANCES: Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population.

Authors

Wang, M; Zhang, R; He, J; Qiu, L; Li, J; Wang, Y; Sun, M; Yang, Y; Wang, J; Yang, J; Qian, J; Jin, L; Ma, H; Wei, Q; Zhou, X

MLA Citation

Wang, M, Zhang, R, He, J, Qiu, L, Li, J, Wang, Y, Sun, M, Yang, Y, Wang, J, Yang, J, Qian, J, Jin, L, Ma, H, Wei, Q, and Zhou, X. "Potentially functional variants of PLCE1 identified by GWASs contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population." PloS one 7.3 (January 2012): e31932-.

PMID

22412849

Source

epmc

Published In

PloS one

Volume

7

Issue

3

Publish Date

2012

Start Page

e31932

DOI

10.1371/journal.pone.0031932

BACKGROUND: HER-2/neu-targeted therapy has been successfully used in advanced gastric cancer, but the role of HER-2/neu in the prognosis of gastric cancer is not yet clear. In this study, we investigated the correlation between HER-2/neu expression and amplification as well as their association with clinic outcomes in patients with curatively resected gastric cancer. METHODS: We constructed tissue microarray blocks containing >70% of gastric cancer tissue and matched adjacent normal gastric tissue for 227 patients. Expression of the HER-2/neu protein in these specimens was analyzed using immunohistochemical staining. Amplification of HER-2/neu was also analyzed for the same samples using fluorescence in situ hybridization. Data on clinicopathological features and relevant prognostic factors in these patients were analyzed. RESULTS: Of the 227 gastric cancer samples, 11.89% were positive for HER-2/neu overexpression/amplification under the new scoring system. HER-2/neu overexpression/amplification was closely correlated to the Lauren type, degree of differentiation, tumor size and lymph node metastasis. HER-2/neu overexpression/amplification predicted poor survival in univariate analysis but not in a Cox proportional hazards model. CONCLUSION: HER-2/neu overexpression/amplification was not an independent predictor for survival in patients with curatively resected gastric cancer.

Authors

Zhou, F; Li, N; Jiang, W; Hua, Z; Xia, L; Wei, Q; Wang, L

MLA Citation

Zhou, F, Li, N, Jiang, W, Hua, Z, Xia, L, Wei, Q, and Wang, L. "Prognosis significance of HER-2/neu overexpression/amplification in Chinese patients with curatively resected gastric cancer after the ToGA clinical trial." World journal of surgical oncology 10 (January 2012): 274-.

PMID

23249720

Source

epmc

Published In

World Journal of Surgical Oncology

Volume

10

Publish Date

2012

Start Page

274

DOI

10.1186/1477-7819-10-274

RAD52 is an important but not well characterized homologous recombination repair gene that can bind to single-stranded DNA ends and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. To evaluate the role of RAD52 variants in the response of tumor cells to platinum agents, we investigated their associations with platinum resistance and prognosis in cervical cancer patients. We enrolled 154 patients with cervical squamous cell carcinoma, who had radical surgery between 2008 and 2009, and genotyped three potentially functional RAD52 variants by the SNaPshot assay. We tested in vitro platinum resistance and RAD52 expression by using the MTT and immunohistochemistry methods, respectively. In 144 cases who had genotyping data, we found that both the rs1051669 variant and RAD52 protein expression were significantly associated with carboplatin resistance (P = 0.024 and 0.028, respectively) and rs10774474 with nedaplatin resistance (P = 0.018). The rs1051669 variant was significantly associated with RAD52 protein expression (adjusted OR = 4.7, 95% CI = 1.4-16.1, P = 0.013). When these three RAD52 variants were combined, progression-free survival was lower in patients who carried at least one (≥1) variant allele compared to those without any of the variant alleles (P = 0.047). Therefore, both RAD52 variants and protein expression can predict platinum resistance, and RAD52 variants appeared to predict prognosis in cervical cancer patients. Large studies are warranted to validate these findings.

Authors

Shi, T-Y; Yang, G; Tu, X-Y; Yang, J-M; Qian, J; Wu, X-H; Zhou, X-Y; Cheng, X; Wei, Q

MLA Citation

Shi, T-Y, Yang, G, Tu, X-Y, Yang, J-M, Qian, J, Wu, X-H, Zhou, X-Y, Cheng, X, and Wei, Q. "RAD52 variants predict platinum resistance and prognosis of cervical cancer." PloS one 7.11 (January 2012): e50461-.

PMID

23209746

Source

epmc

Published In

PloS one

Volume

7

Issue

11

Publish Date

2012

Start Page

e50461

DOI

10.1371/journal.pone.0050461

BACKGROUND: Non-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population. METHOD: We used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: We observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49-3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41-2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes. CONCLUSIONS: The polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

Authors

Zhang, Y; Wang, M-Y; He, J; Wang, J-C; Yang, Y-J; Jin, L; Chen, Z-Y; Ma, X-J; Sun, M-H; Xia, K-Q; Hong, X-N; Wei, Q-Y; Zhou, X-Y

MLA Citation

Zhang, Y, Wang, M-Y, He, J, Wang, J-C, Yang, Y-J, Jin, L, Chen, Z-Y, Ma, X-J, Sun, M-H, Xia, K-Q, Hong, X-N, Wei, Q-Y, and Zhou, X-Y. "Tumor necrosis factor-α induced protein 8 polymorphism and risk of non-Hodgkin's lymphoma in a Chinese population: a case-control study." PloS one 7.5 (January 2012): e37846-.

PMID

22666399

Source

epmc

Published In

PloS one

Volume

7

Issue

5

Publish Date

2012

Start Page

e37846

DOI

10.1371/journal.pone.0037846

Recent studies reported associations of the relative telomere length (RTL) and TERT variants with risk of several cancers, which have not been comprehensively investigated in squamous cell carcinoma of the head and neck (SCCHN).We detected RTL in peripheral blood lymphocytes and genotyped six selected functional single-nucleotide polymorphisms (SNP) of the TERT gene in 888 SCCHN cases and 885 cancer-free controls of non-Hispanic whites.Overall, we did not observe significant associations between RTL and SCCHN risk (adjusted OR = 0.97; 95% CI = 0.80-1.17 for below versus above the median; P(trend) = 0.618) nor between the six TERT SNPs and SCCHN risk. We also found no associations between RTL and TERT SNPs.Our results suggest that RTL and TERT functional polymorphisms may not play a major role in the etiology of SCCHN. Large prospective studies are needed to validate our findings.Although our results suggest no association among RTL, TERT functional polymorphisms, and SCCHN risk, this study may contribute to future meta-analysis.

Authors

Liu, Z; Ma, H; Wei, S; Li, G; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Ma, H, Wei, S, Li, G, Sturgis, EM, and Wei, Q. "Telomere length and TERT functional polymorphisms are not associated with risk of squamous cell carcinoma of the head and neck." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20.12 (December 2011): 2642-2645.

PMID

21994403

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

20

Issue

12

Publish Date

2011

Start Page

2642

End Page

2645

DOI

10.1158/1055-9965.epi-11-0890

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.

Authors

Amos, CI; Wang, L-E; Lee, JE; Gershenwald, JE; Chen, WV; Fang, S; Kosoy, R; Zhang, M; Qureshi, AA; Vattathil, S; Schacherer, CW; Gardner, JM; Wang, Y; Bishop, DT; Barrett, JH; GenoMEL Investigators, ; MacGregor, S; Hayward, NK; Martin, NG; Duffy, DL; Q-Mega Investigators, ; Mann, GJ; Cust, A; Hopper, J; AMFS Investigators, ; Brown, KM; Grimm, EA; Xu, Y; Han, Y; Jing, K; McHugh, C; Laurie, CC; Doheny, KF; Pugh, EW; Seldin, MF; Han, J; Wei, Q

MLA Citation

Amos, CI, Wang, L-E, Lee, JE, Gershenwald, JE, Chen, WV, Fang, S, Kosoy, R, Zhang, M, Qureshi, AA, Vattathil, S, Schacherer, CW, Gardner, JM, Wang, Y, Bishop, DT, Barrett, JH, GenoMEL Investigators, , MacGregor, S, Hayward, NK, Martin, NG, Duffy, DL, Q-Mega Investigators, , Mann, GJ, Cust, A, Hopper, J, AMFS Investigators, , Brown, KM, Grimm, EA, Xu, Y, Han, Y, Jing, K, McHugh, C, Laurie, CC, Doheny, KF, Pugh, EW, Seldin, MF, Han, J, and Wei, Q. "Genome-wide association study identifies novel loci predisposing to cutaneous melanoma." Human molecular genetics 20.24 (December 2011): 5012-5023.

PMID

21926416

Source

epmc

Published In

Human Molecular Genetics

Volume

20

Issue

24

Publish Date

2011

Start Page

5012

End Page

5023

DOI

10.1093/hmg/ddr415

Although the role of TNFAIP2 is still unclear, it is an important gene involved in apoptosis, and there are single-nucleotide polymorphisms (SNPs) at its microRNA (miRNA)-binding sites that could modulate miRNA target gene function. In this study, we evaluated associations of four selected SNPs (rs8126 T > C, rs710100 G > A, rs1052912 G > A and rs1052823 G > T) in the miRNA-binding sites of the 3' untranslated region (UTR) with squamous cell carcinoma of the head and neck (SCCHN) risk in 1077 patients with SCCHN and 1073 cancer-free controls in a non-Hispanic White population. We found that, compared with the rs8126 TT genotype, the variant C allele were associated with increased SCCHN risk in an allele dose-response manner (adjusted odds ratio = 1.48 and 95% confidence interval = 1.06-2.05 for CC, respectively; P(trend) = 0.009). No significant associations were seen for the other three SNPs (rs710100 G > A, rs1052912 G > A and rs1052823 G > T). Additionally, we identified that the rs8126 T > C SNP is within the miR-184 seed binding region in the 3' UTR of TNFAIP2. Further functional analyses showed that the rs8126 variant C allele led to significantly lower luciferase activity, compared with the T allele. In the genotype-phenotype correlation analysis of peripheral blood mononuclear cells from 64 SCCHN patients, the rs8126 CC genotype was associated with reduced expression of TNFAIP2 messenger RNA. Taken together, these findings indicate that the miR-184 binding site SNP (rs8126 T > C) in the 3' UTR of TNFAIP2 is functional by modulating TNFAIP2 expression and contributes to SCCHN susceptibility. Larger replication studies are needed to confirm our findings.

Authors

Liu, Z; Wei, S; Ma, H; Zhao, M; Myers, JN; Weber, RS; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Wei, S, Ma, H, Zhao, M, Myers, JN, Weber, RS, Sturgis, EM, and Wei, Q. "A functional variant at the miR-184 binding site in TNFAIP2 and risk of squamous cell carcinoma of the head and neck." Carcinogenesis 32.11 (November 2011): 1668-1674.

PMID

21934093

Source

epmc

Published In

Carcinogenesis

Volume

32

Issue

11

Publish Date

2011

Start Page

1668

End Page

1674

DOI

10.1093/carcin/bgr209

To explore whether functional single nucleotide polymorphisms (SNPs) of base-excision repair genes are predictors of radiation treatment-related pneumonitis (RP), we investigated associations between functional SNPs of ADPRT, APEX1, and XRCC1 and RP development.We genotyped SNPs of ADPRT (rs1136410 [V762A]), XRCC1 (rs1799782 [R194W], rs25489 [R280H], and rs25487 [Q399R]), and APEX1 (rs1130409 [D148E]) in 165 patients with non-small cell lung cancer (NSCLC) who received definitive chemoradiation therapy. Results were assessed by both Logistic and Cox regression models for RP risk. Kaplan-Meier curves were generated for the cumulative RP probability by the genotypes.We found that SNPs of XRCC1 Q399R and APEX1 D148E each had a significant effect on the development of Grade ≥2 RP (XRCC1: AA vs. GG, adjusted hazard ratio [HR] = 0.48, 95% confidence interval [CI], 0.24-0.97; APEX1: GG vs. TT, adjusted HR = 3.61, 95% CI, 1.64-7.93) in an allele-dose response manner (Trend tests: p = 0.040 and 0.001, respectively). The number of the combined protective XRCC1 A and APEX1 T alleles (from 0 to 4) also showed a significant trend of predicting RP risk (p = 0.001).SNPs of the base-excision repair genes may be biomarkers for susceptibility to RP. Larger prospective studies are needed to validate our findings.

Authors

Yin, M; Liao, Z; Liu, Z; Wang, L-E; Gomez, D; Komaki, R; Wei, Q

MLA Citation

Yin, M, Liao, Z, Liu, Z, Wang, L-E, Gomez, D, Komaki, R, and Wei, Q. "Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy." International journal of radiation oncology, biology, physics 81.3 (November 2011): e67-e73.

PMID

21420246

Source

epmc

Published In

International Journal of Radiation Oncology, Biology, Physics

Volume

81

Issue

3

Publish Date

2011

Start Page

e67

End Page

e73

DOI

10.1016/j.ijrobp.2010.11.079

PURPOSE: We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay. RESULTS: Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10-0.91; P=0.033; multivariate HR 0.29; 95% CI, 0.09-0.97; P=0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period. CONCLUSIONS: The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials.

Authors

Lopez Guerra, JL; Wei, Q; Yuan, X; Gomez, D; Liu, Z; Zhuang, Y; Yin, M; Li, M; Wang, L-E; Cox, JD; Liao, Z

MLA Citation

Lopez Guerra, JL, Wei, Q, Yuan, X, Gomez, D, Liu, Z, Zhuang, Y, Yin, M, Li, M, Wang, L-E, Cox, JD, and Liao, Z. "Functional promoter rs2868371 variant of HSPB1 associates with radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with radio(chemo)therapy." Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 101.2 (November 2011): 271-277.

PMID

21937138

Source

epmc

Published In

Radiotherapy & Oncology

Volume

101

Issue

2

Publish Date

2011

Start Page

271

End Page

277

DOI

10.1016/j.radonc.2011.08.039

Platinum-based regimens are the standard chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC). DNA repair capacity (DRC) in tumor cells plays an important role in resistance to platinum-based drugs. We have previously reported that efficient DRC, as assessed by an in vitro lymphocyte-based assay, was a determinant of poor survival in patients with NSCLC in a relatively small data set. In this larger independent study of 591 patients with NSCLC, we further evaluated whether DRC in peripheral lymphocytes predicts survival of patients with NSCLC who receive platinum-based chemotherapy.All patients were recruited at The University of Texas MD Anderson Cancer Center and donated blood samples before the start of any chemotherapy. We measured DRC in cultured T lymphocytes by using the host-cell reactivation assay, and we assessed associations between DRC in peripheral lymphocytes and survival of patients with NSCLC who were treated with first-line platinum-based chemotherapy.We found an inverse association between DRC in peripheral lymphocytes and patient survival. Compared with patients in the low tertile of DRC, patients with NSCLC in the high tertile of DRC had significantly worse overall and 3-year survival (adjusted hazard ratio [HR], 1.33; 95% CI, 1.04 to 1.71; P = .023; and HR, 1.35; 95% CI, 1.04 to 1.76; P = .025, respectively). This trend was more pronounced in patients with early-stage tumors, adenocarcinoma, or squamous cell carcinoma.We confirmed that DRC in peripheral lymphocytes is an independent predictor of survival for patients with NSCLC treated with platinum-based chemotherapy.

Authors

Wang, L-E; Yin, M; Dong, Q; Stewart, DJ; Merriman, KW; Amos, CI; Spitz, MR; Wei, Q

MLA Citation

Wang, L-E, Yin, M, Dong, Q, Stewart, DJ, Merriman, KW, Amos, CI, Spitz, MR, and Wei, Q. "DNA repair capacity in peripheral lymphocytes predicts survival of patients with non-small-cell lung cancer treated with first-line platinum-based chemotherapy." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 29.31 (November 2011): 4121-4128.

PMID

21947825

Source

epmc

Published In

Journal of Clinical Oncology

Volume

29

Issue

31

Publish Date

2011

Start Page

4121

End Page

4128

DOI

10.1200/jco.2010.34.3616

H2AFX, a histone H2A gene family member X, is a key component in the detection of and response to DNA double-strand breaks (DSBs) caused by ionizing radiation (IR), a known risk factor for glioma. Thus, genetic variants in the H2AFX promoter region that may result in abnormal protein expression could confer susceptibility to glioma. In this case-control study, we genotyped three common single-nucleotide polymorphisms (SNPs) (rs643788, rs8551, and rs2509851) in the H2AFX promoter region in 669 adult glioma patients and 638 cancer-free controls. The associations between each SNP or haplotype and glioma risk were estimated by calculating odds ratios (ORs) and the corresponding 95% confidence interval (CI) using unconditional logistic regression models, with adjustment for age and sex. The H2AFX rs643788 A variant genotypes were significantly associated with reduced risk of glioma (GA versus GG: adjusted OR = 0.72, 95% CI = 0.56-0.94; GA/AA versus GG: adjusted OR = 0.75, 95% CI = 0.59-0.94), compared with the common GG genotype. Furthermore, this decreased risk was more evident among those aged ≥ 45 years (adjusted OR = 0.64, 95% CI = 0.45-0.90), male subjects (adjusted OR = 0.70, 95% CI = 0.50-0.96), and patients with glioblastoma (adjusted OR = 0.66, 95% CI = 0.46-0.94). These results suggest that a common variant in the H2AFX promoter region may modulate risk of glioma, particularly for adult glioma. However, our findings need to be replicated in other independent populations.

Authors

Fan, W; Zhou, K; Zhao, Y; Wu, W; Chen, H; Jin, L; Chen, G; Shi, J; Wei, Q; Zhang, T; Du, G; Mao, Y; Lu, D; Zhou, L

MLA Citation

Fan, W, Zhou, K, Zhao, Y, Wu, W, Chen, H, Jin, L, Chen, G, Shi, J, Wei, Q, Zhang, T, Du, G, Mao, Y, Lu, D, and Zhou, L. "Possible association between genetic variants in the H2AFX promoter region and risk of adult glioma in a Chinese Han population." Journal of neuro-oncology 105.2 (November 2011): 211-218.

PMID

21512825

Source

epmc

Published In

Journal of Neuro-Oncology

Volume

105

Issue

2

Publish Date

2011

Start Page

211

End Page

218

DOI

10.1007/s11060-011-0586-5

The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy.We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629) and -1031 T>C (rs1799964); TNFRSF1B +676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N2-3 vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T3-4 vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03).Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.

Authors

Guan, X; Liao, Z; Ma, H; Qian, J; Liu, Z; Yuan, X; Gomez, D; Komaki, R; Wang, L-E; Wei, Q

MLA Citation

Guan, X, Liao, Z, Ma, H, Qian, J, Liu, Z, Yuan, X, Gomez, D, Komaki, R, Wang, L-E, and Wei, Q. "TNFRSF1B +676 T>G polymorphism predicts survival of non-small cell lung cancer patients treated with chemoradiotherapy." BMC cancer 11 (October 14, 2011): 447-.

PMID

21995493

Source

epmc

Published In

BMC Cancer

Volume

11

Publish Date

2011

Start Page

447

DOI

10.1186/1471-2407-11-447

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.

Authors

Macgregor, S; Montgomery, GW; Liu, JZ; Zhao, ZZ; Henders, AK; Stark, M; Schmid, H; Holland, EA; Duffy, DL; Zhang, M; Painter, JN; Nyholt, DR; Maskiell, JA; Jetann, J; Ferguson, M; Cust, AE; Jenkins, MA; Whiteman, DC; Olsson, H; Puig, S; Bianchi-Scarrà, G; Hansson, J; Demenais, F; Landi, MT; Dębniak, T; Mackie, R; Azizi, E; Bressac-de Paillerets, B; Goldstein, AM; Kanetsky, PA; Gruis, NA; Elder, DE; Newton-Bishop, JA; Bishop, DT; Iles, MM; Helsing, P; Amos, CI; Wei, Q; Wang, L-E; Lee, JE et al.

MLA Citation

Macgregor, S, Montgomery, GW, Liu, JZ, Zhao, ZZ, Henders, AK, Stark, M, Schmid, H, Holland, EA, Duffy, DL, Zhang, M, Painter, JN, Nyholt, DR, Maskiell, JA, Jetann, J, Ferguson, M, Cust, AE, Jenkins, MA, Whiteman, DC, Olsson, H, Puig, S, Bianchi-Scarrà, G, Hansson, J, Demenais, F, Landi, MT, Dębniak, T, Mackie, R, Azizi, E, Bressac-de Paillerets, B, Goldstein, AM, Kanetsky, PA, Gruis, NA, Elder, DE, Newton-Bishop, JA, Bishop, DT, Iles, MM, Helsing, P, Amos, CI, Wei, Q, Wang, L-E, and Lee, JE et al. "Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3." Nature genetics 43.11 (October 9, 2011): 1114-1118.

PMID

21983785

Source

epmc

Published In

Nature Genetics

Volume

43

Issue

11

Publish Date

2011

Start Page

1114

End Page

1118

DOI

10.1038/ng.958

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.

Authors

Barrett, JH; Iles, MM; Harland, M; Taylor, JC; Aitken, JF; Andresen, PA; Akslen, LA; Armstrong, BK; Avril, M-F; Azizi, E; Bakker, B; Bergman, W; Bianchi-Scarrà, G; Bressac-de Paillerets, B; Calista, D; Cannon-Albright, LA; Corda, E; Cust, AE; Dębniak, T; Duffy, D; Dunning, AM; Easton, DF; Friedman, E; Galan, P; Ghiorzo, P; Giles, GG; Hansson, J; Hocevar, M; Höiom, V; Hopper, JL; Ingvar, C; Janssen, B; Jenkins, MA; Jönsson, G; Kefford, RF; Landi, G; Landi, MT; Lang, J; Lubiński, J; Mackie, R et al.

MLA Citation

Barrett, JH, Iles, MM, Harland, M, Taylor, JC, Aitken, JF, Andresen, PA, Akslen, LA, Armstrong, BK, Avril, M-F, Azizi, E, Bakker, B, Bergman, W, Bianchi-Scarrà, G, Bressac-de Paillerets, B, Calista, D, Cannon-Albright, LA, Corda, E, Cust, AE, Dębniak, T, Duffy, D, Dunning, AM, Easton, DF, Friedman, E, Galan, P, Ghiorzo, P, Giles, GG, Hansson, J, Hocevar, M, Höiom, V, Hopper, JL, Ingvar, C, Janssen, B, Jenkins, MA, Jönsson, G, Kefford, RF, Landi, G, Landi, MT, Lang, J, Lubiński, J, and Mackie, R et al. "Genome-wide association study identifies three new melanoma susceptibility loci." Nature genetics 43.11 (October 9, 2011): 1108-1113.

PMID

21983787

Source

epmc

Published In

Nature Genetics

Volume

43

Issue

11

Publish Date

2011

Start Page

1108

End Page

1113

DOI

10.1038/ng.959

Both p53 tumor suppressor and murine double minute 2 (MDM2) oncoprotein are crucial in carcinogenesis. We hypothesized that MDM2 promoter single nucleotide polymorphisms (SNPs) SNP309 T > G, A2164G, and p53 codon 72 are associated with risk and age at onset of squamous cell carcinoma of head and neck (SCCHN). We genotyped these SNPs in a study of 1,083 Caucasian SCCHN cases and 1,090 cancer-free controls. Although none of these SNPs individually had a significant effect on risk of SCCHN, nor did their combined putative risk genotypes (i.e., MDM2 SNP309 GT + GG, 2164 AA, and p53 codon 72 CC), we found that individuals with two to three risk genotypes had significantly increased risk of non-oropharyngeal cancer (OR = 1.42; 95% CI = 1.07-1.88). This increased risk was more pronounced among young subjects, men, smokers, and drinkers. In addition, female patients carrying the MDM2 SNP309 GT and GG genotypes showed a 3-yr (56.7 yr) and 9-yr (51.2 yr) earlier age at onset of non-oropharyngeal cancer (P(trend) = 0.007), respectively, compared with those carrying the TT genotype (60.1 yr). The youngest age (42.5 yr) at onset of non-oropharyngeal cancer was observed in female patients with the combined MDM2 SNP309 GG and p53 codon 72 CC genotypes. The findings suggest that MDM2 SNP309, A2164G, and p53 codon 72 SNPs may collectively contribute to non-oropharyngeal cancer risk and that MDM2 SNP309 individually or in combination with p53 codon 72 may accelerate the development of non-oropharyngeal cancer in women. Further studies with large sample sizes are warranted to validate these results.

Authors

Yu, H; Huang, Y-J; Liu, Z; Wang, L-E; Li, G; Sturgis, EM; Johnson, DG; Wei, Q

MLA Citation

Yu, H, Huang, Y-J, Liu, Z, Wang, L-E, Li, G, Sturgis, EM, Johnson, DG, and Wei, Q. "Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck." Molecular carcinogenesis 50.9 (September 2011): 697-706.

PMID

21656578

Source

epmc

Published In

Molecular Carcinogenesis

Volume

50

Issue

9

Publish Date

2011

Start Page

697

End Page

706

DOI

10.1002/mc.20806

Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors.We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models.ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (≥ 25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers.The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.

Authors

Lubin, JH; Muscat, J; Gaudet, MM; Olshan, AF; Curado, MP; Dal Maso, L; Wünsch-Filho, V; Sturgis, EM; Szeszenia-Dabrowska, N; Castellsague, X; Zhang, Z-F; Smith, E; Fernandez, L; Matos, E; Franceschi, S; Fabianova, E; Rudnai, P; Purdue, MP; Mates, D; Wei, Q; Herrero, R; Kelsey, K; Morgenstern, H; Shangina, O; Koifman, S; Lissowska, J; Levi, F; Daudt, AW; Neto, JE; Chen, C; Lazarus, P; Winn, DM; Schwartz, SM; Boffetta, P; Brennan, P; Menezes, A; La Vecchia, C; McClean, M; Talamini, R; Rajkumar, T et al.

MLA Citation

Lubin, JH, Muscat, J, Gaudet, MM, Olshan, AF, Curado, MP, Dal Maso, L, Wünsch-Filho, V, Sturgis, EM, Szeszenia-Dabrowska, N, Castellsague, X, Zhang, Z-F, Smith, E, Fernandez, L, Matos, E, Franceschi, S, Fabianova, E, Rudnai, P, Purdue, MP, Mates, D, Wei, Q, Herrero, R, Kelsey, K, Morgenstern, H, Shangina, O, Koifman, S, Lissowska, J, Levi, F, Daudt, AW, Neto, JE, Chen, C, Lazarus, P, Winn, DM, Schwartz, SM, Boffetta, P, Brennan, P, Menezes, A, La Vecchia, C, McClean, M, Talamini, R, and Rajkumar, T et al. "An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies." Cancer causes & control : CCC 22.9 (September 2011): 1217-1231.

PMID

21744095

Source

epmc

Published In

Cancer Causes & Control

Volume

22

Issue

9

Publish Date

2011

Start Page

1217

End Page

1231

DOI

10.1007/s10552-011-9792-x

We conducted a genome-wide association study on cutaneous basal cell carcinoma (BCC) among 2045 cases and 6013 controls of European ancestry, with follow-up replication in 1426 cases and 4845 controls. A non-synonymous SNP in the MC1R gene (rs1805007 encoding Arg151Cys substitution), a previously well-documented pigmentation gene, showed the strongest association with BCC risk in the discovery set (rs1805007[T]: OR (95% CI) for combined discovery set and replication set [1.55 (1.45-1.66); P= 4.3 × 10(-17)]. We identified that an SNP rs12210050 at 6p25 near the EXOC2 gene was associated with an increased risk of BCC [rs12210050[T]: combined OR (95% CI), 1.24 (1.17-1.31); P= 9.9 × 10(-10)]. In the locus on 13q32 near the UBAC2 gene encoding ubiquitin-associated domain-containing protein 2, we also identified a variant conferring susceptibility to BCC [rs7335046 [G]; combined OR (95% CI), 1.26 (1.18-1.34); P= 2.9 × 10(-8)]. We further evaluated the associations of these two novel SNPs (rs12210050 and rs7335046) with squamous cell carcinoma (SCC) risk as well as melanoma risk. We found that both variants, rs12210050[T] [OR (95% CI), 1.35 (1.16-1.57); P= 7.6 × 10(-5)] and rs7335046 [G] [OR (95% CI), 1.21 (1.02-1.44); P= 0.03], were associated with an increased risk of SCC. These two variants were not associated with melanoma risk. We conclude that 6p25 and 13q32 are novel loci conferring susceptibility to non-melanoma skin cancer.

Authors

Nan, H; Xu, M; Kraft, P; Qureshi, AA; Chen, C; Guo, Q; Hu, FB; Curhan, G; Amos, CI; Wang, L-E; Lee, JE; Wei, Q; Hunter, DJ; Han, J

MLA Citation

Nan, H, Xu, M, Kraft, P, Qureshi, AA, Chen, C, Guo, Q, Hu, FB, Curhan, G, Amos, CI, Wang, L-E, Lee, JE, Wei, Q, Hunter, DJ, and Han, J. "Genome-wide association study identifies novel alleles associated with risk of cutaneous basal cell carcinoma and squamous cell carcinoma." Human molecular genetics 20.18 (September 2011): 3718-3724.

PMID

21700618

Source

epmc

Published In

Human Molecular Genetics

Volume

20

Issue

18

Publish Date

2011

Start Page

3718

End Page

3724

DOI

10.1093/hmg/ddr287

Genetic variations in the CYP2A6 nicotine metabolic gene and the CHRNA5-CHRNA3-CHRNB4 (CHRNA5-A3-B4) nicotinic gene cluster have been independently associated with lung cancer. With genotype data from ever-smokers of European ancestry (417 lung cancer patients and 443 control subjects), we investigated the relative and combined associations of polymorphisms in these two genes with smoking behavior and lung cancer risk. Kruskal-Wallis tests were used to compare smoking variables among the different genotype groups, and odds ratios (ORs) for cancer risk were estimated using logistic regression analysis. All statistical tests were two-sided. Cigarette consumption (P < .001) and nicotine dependence (P = .036) were the highest in the combined CYP2A6 normal metabolizers and CHRNA5-A3-B4 AA (tag single-nucleotide polymorphism rs1051730 G>A) risk group. The combined risk group also exhibited the greatest lung cancer risk (OR = 2.03; 95% confidence interval [CI] = 1.21 to 3.40), which was even higher among those who smoked 20 or fewer cigarettes per day (OR = 3.03; 95% CI = 1.38 to 6.66). Variation in CYP2A6 and CHRNA5-A3-B4 was independently and additively associated with increased cigarette consumption, nicotine dependence, and lung cancer risk. CYP2A6 and CHRNA5-A3-B4 appear to be more strongly associated with smoking behaviors and lung cancer risk, respectively.

Authors

Wassenaar, CA; Dong, Q; Wei, Q; Amos, CI; Spitz, MR; Tyndale, RF

MLA Citation

Wassenaar, CA, Dong, Q, Wei, Q, Amos, CI, Spitz, MR, and Tyndale, RF. "Relationship between CYP2A6 and CHRNA5-CHRNA3-CHRNB4 variation and smoking behaviors and lung cancer risk." JNCI Journal of the National Cancer Institute 103.17 (September 2011): 1342-1346.

PMID

21747048

Source

epmc

Published In

Journal of the National Cancer Institute

Volume

103

Issue

17

Publish Date

2011

Start Page

1342

End Page

1346

DOI

10.1093/jnci/djr237

To investigate the association between chromosome 8p11 (CHRNB3-CHRNA6) polymorphisms and lung cancer susceptibility in Chinese Han population, we genotyped 6 tag SNPs variants of this region among 784 patients with lung cancer and 782 age- and sex-matched cancer-free control participants to screen for any risk-associated SNPs. The results revealed that rs16891561 TT genotype had a protective effect against lung cancer in people over 60 years old (adjusted OR=0.42, 95% CI=0.20-0.88; P=0.022), female groups (adjusted OR=0.34, 95% CI=0.13-0.87; P=0.025), and non-smoking people (adjusted OR=0.32, 95% CI=0.13-079; P=0.013). Additionally, rs4236926 TT genotype had a protective effect against lung cancer in people over 60 years old (adjusted OR=0.48, 95% CI=0.23-0.99; P=0.048) and non-smoking people (adjusted OR=0.32, 95% CI=0.13-0.80; P=0.014). According to pathological type of lung cancer, these two SNPs were associated with adenocarcinomas susceptibility. As to cumulative effect of rs4236926 and rs16891561, in non-smokers strata, lung cancer risk was significantly reduced in those who had 3-4 mutant alleles (adjusted OR=0.29, 95% CI=0.11-0.71; P=0.007). Furthermore, people containing 3-4 mutant alleles had lower level of smoking doses (mean pack-year=13.2) compared with others. In conclusion, 8p11 (CHRNB3-CHRNA6) polymorphisms are related to smoking behavior and lung cancer susceptibility in Chinese Han population.

Authors

Zhang, X-B; Zhao, Z-H; Chen, H-Y; Wang, J-C; Qian, J; Yang, Y-J; Wei, Q-Y; Huang, J; Lu, D-R

MLA Citation

Zhang, X-B, Zhao, Z-H, Chen, H-Y, Wang, J-C, Qian, J, Yang, Y-J, Wei, Q-Y, Huang, J, and Lu, D-R. "[Human chromosome 8p11 (CHRNB3-CHRNA6) region gene polymorphisms and susceptibility to lung cancer in Chinese Han population]." Yi chuan = Hereditas 33.8 (August 2011): 886-894.

PMID

21831805

Source

epmc

Published In

Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji.

Volume

33

Issue

8

Publish Date

2011

Start Page

886

End Page

894

DOI

10.3724/sp.j.1005.2011.00886

Mouse double minute 4 (MDM4), a homolog of MDM2, is one of the key negative regulators of p53, and its amplification or overexpression contributes to carcinogenesis by inhibiting the p53 tumor suppressor activity. We investigated the association between MDM4 polymorphisms and the risk of squamous cell carcinoma of the head and neck (SCCHN).We genotyped three MDM4 tagging polymorphisms, two in the 3' untranslated region (rs11801299G>A and rs10900598G>T) and one in intron 1 (rs1380576C>G), in a case-control study of 1075 non-Hispanic white SCCHN patients and 1079 cancer-free controls, and evaluated their associations with SCCHN risk.Although none of these three polymorphisms individually had a statistically significant effect on the risk of SCCHN, nor did their combined number of putative risk genotypes (i.e. rs11801299GG, rs1380576CG+GG, and rs10900598GG) [odds ratio (OR)=1.16; 95% confidence interval (95% CI) =0.93-1.45], we found that individuals with 1-3 risk genotypes had statistically significant increased risk of oropharyngeal cancer (OR=1.32; 95% CI=1.00-1.73), particularly for those with T1-2 stage (OR=1.40; 95% CI=1.02-1.94), those with regional lymph node metastases (N1-3) (OR=1.44; 95% CI=1.07-1.95), and those with late stages (III and IV) (OR=1.34; 95% CI=1.01-1.77).These results suggest that the joint effect of MDM4 variants may contribute to the risk of oropharyngeal cancer in non-Hispanic whites. Additional studies are warranted to unravel whether the particular stage distribution of oropharyngeal cancer with the strongest association (T1-2, N1-3, and III-IV) is a possible link with human papillomavirus-related oropharyngeal cancers.

Authors

Yu, H; Wang, L-E; Liu, Z; Wei, S; Li, G; Sturgis, EM; Wei, Q

MLA Citation

Yu, H, Wang, L-E, Liu, Z, Wei, S, Li, G, Sturgis, EM, and Wei, Q. "Polymorphisms of MDM4 and risk of squamous cell carcinoma of the head and neck." Pharmacogenetics and genomics 21.7 (July 2011): 388-396.

PMID

21540763

Source

epmc

Published In

Pharmacogenetics and Genomics

Volume

21

Issue

7

Publish Date

2011

Start Page

388

End Page

396

DOI

10.1097/fpc.0b013e32834632e4

We conducted a genome-wide association study on the number of melanocytic nevi reported by 9136 individuals of European ancestry, with follow-up replication in 3581 individuals. We identified the nidogen 1 (NID1) gene on 1q42 associated with nevus count (two linked single nucleotide polymorphisms with r(2) > 0.9: rs3768080 A allele associated with reduced count, P = 6.5 × 10(-8); and rs10754833 T allele associated with reduced count, P = 1.5 × 10(-7)). We further determined that the rs10754833 [T] was associated with a decreased melanoma risk in 2368 melanoma cases and 7432 controls [for CT genotype: odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, P = 0.04; for TT genotype: OR = 0.84, 95% CI = 0.71-0.98, P = 0.03]. Expression level of the NID1 locus was 2-fold higher for the rs10754833 T allele carriers than that with the CC genotype (P = 0.017) in the 87 HapMap CEU cell lines. The NID1 gene is a biologically plausible locus for nevogenesis and melanoma development, with decreased expression levels of NID1 in benign nevi (P = 3.5 × 10(-6)) and in primary melanoma (P = 4.6 × 10(-4)) compared with the normal skin.

Authors

Nan, H; Xu, M; Zhang, J; Zhang, M; Kraft, P; Qureshi, AA; Chen, C; Guo, Q; Hu, FB; Rimm, EB; Curhan, G; Song, Y; Amos, CI; Wang, L-E; Lee, JE; Wei, Q; Hunter, DJ; Han, J

MLA Citation

Nan, H, Xu, M, Zhang, J, Zhang, M, Kraft, P, Qureshi, AA, Chen, C, Guo, Q, Hu, FB, Rimm, EB, Curhan, G, Song, Y, Amos, CI, Wang, L-E, Lee, JE, Wei, Q, Hunter, DJ, and Han, J. "Genome-wide association study identifies nidogen 1 (NID1) as a susceptibility locus to cutaneous nevi and melanoma risk." Human molecular genetics 20.13 (July 2011): 2673-2679.

PMID

21478494

Source

epmc

Published In

Human Molecular Genetics

Volume

20

Issue

13

Publish Date

2011

Start Page

2673

End Page

2679

DOI

10.1093/hmg/ddr154

Phospholipase C epsilon 1 (PLCE1) (an effector of Ras) belonging to the phospholipase family plays crucial roles in carcinogenesis and progression of several cancers, including squamous cell carcinoma of the head and neck (SCCHN). A single nucleotide polymorphism (SNP, rs2274223) in PLCE1 has been identified as a novel susceptibility locus in genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) that share similar risk factors with SCCHN. Therefore, we investigated the association between potentially functional SNPs in PLCE1 and susceptibility to SCCHN.We genotyped three potentially functional SNPs (rs2274223A/G, rs3203713A/G and rs11599672T/G) of PLCE1 in 1,098 SCCHN patients and 1,090 controls matched by age and sex in a non-Hispanic white population.Although none of three SNPs was alone significantly associated with overall risk of SCCHN, their combined effects of risk alleles (rs2274223G, rs3203713G and rs11599672G) were found to be associated with risk of SCCHN in a locus-dose effect manner (Ptrend=0.046), particularly for non-oropharyngeal tumors (Ptrend=0.017); specifically, rs2274223 was associated with a significantly increased risk (AG vs. AA: adjusted OR=1.29, 95% CI=1.01-1.64; AG/GG vs. AA: adjusted OR=1.30, 95% CI=1.03-1.64), while rs11599672 was associated with a significantly decreased risk (GG vs. TT: adjusted OR=0.54, 95% CI=0.34-0.86; TG/GG vs. TT: adjusted OR=0.76, 95% CI=0.61-0.95).Our findings suggest that PLCE1 variants may have an effect on risk of SCCHN associated with tobacco and alcohol exposure, particularly for those tumors arising at non-oropharyngeal sites. These findings, although need to be validated by larger studies, are consistent with those in esophageal and gastric cancers.

Authors

Ma, H; Wang, L-E; Liu, Z; Sturgis, EM; Wei, Q

MLA Citation

Ma, H, Wang, L-E, Liu, Z, Sturgis, EM, and Wei, Q. "Association between novel PLCE1 variants identified in published esophageal cancer genome-wide association studies and risk of squamous cell carcinoma of the head and neck." BMC cancer 11 (June 20, 2011): 258-.

PMID

21689432

Source

epmc

Published In

BMC Cancer

Volume

11

Publish Date

2011

Start Page

258

DOI

10.1186/1471-2407-11-258

An emerging epidemic of human papillomavirus (HPV)-associated oropharyngeal cancer has been proposed. The purpose of this study was for us to compare the sexual behaviors of patients with squamous cell carcinoma of the oropharynx (SCCOP) and patients with squamous cell carcinoma of non-oropharyngeal (SCCNOP) head and neck sites to expand our understanding of sexual behavior as a risk factor for HPV-associated head and neck cancer.The sexual history of 165 patients with SCCOP and 87 patients with SCCNOP was determined in a hospital-based case-to-case comparison study.Patients with SCCOP were significantly more likely than patients with SCCNOP to have had >9 lifetime sex partners (odds ratio [OR], 39.2; 95% confidence interval [CI], 8.2-187.3), to have engaged in oral-genital sex (OR, 3.5; 95% CI, 1.1-11.1), and to have had >4 oral-genital sex partners (OR, 8.6; 95% CI, 2.2-33.4).The findings of this study suggest that some risk factors are site-specific and provide further evidence that certain sexual behaviors increase the risk of HPV-associated SCCOP.

Authors

Dahlstrom, KR; Li, G; Tortolero-Luna, G; Wei, Q; Sturgis, EM

MLA Citation

Dahlstrom, KR, Li, G, Tortolero-Luna, G, Wei, Q, and Sturgis, EM. "Differences in history of sexual behavior between patients with oropharyngeal squamous cell carcinoma and patients with squamous cell carcinoma at other head and neck sites." Head & neck 33.6 (June 2011): 847-855.

PMID

20737488

Source

epmc

Published In

Head & Neck: Journal for the Sciences & Specialties of the Head and Neck

Volume

33

Issue

6

Publish Date

2011

Start Page

847

End Page

855

DOI

10.1002/hed.21550

The nucleotide excision repair (NER) pathway modulates platinum-based chemotherapeutic efficacy by removing drug-induced DNA damage.To summarize published data on the association between NER genes and responses to platinum-based chemotherapies in non-small cell lung cancer (NSCLC), we performed a meta-analysis of 17 published studies of ERCC1 C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn polymorphisms, including 2097 cancer patients. Primary outcomes included objective response (TR) (i.e., complete response+partial response vs. stable disease+progressive disease), progression-free survival (PFS) and overall survival (OS). We calculated odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) to estimate the risk or hazard.We found that none of the ERCC1 C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn polymorphisms alone was statistically significantly associated with objective response, PFS and OS in NSCLC patients.There is no evidence to support the use of NER ERCC1 C118T/C8092A and ERCC2 Lys751Gln/Asp312Asn polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC.

Authors

Yin, M; Yan, J; Voutsina, A; Tibaldi, C; Christiani, DC; Heist, RS; Rosell, R; Booton, R; Wei, Q

MLA Citation

Yin, M, Yan, J, Voutsina, A, Tibaldi, C, Christiani, DC, Heist, RS, Rosell, R, Booton, R, and Wei, Q. "No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta-analysis." Lung cancer (Amsterdam, Netherlands) 72.3 (June 2011): 370-377.

PMID

21075476

Source

epmc

Published In

Lung Cancer

Volume

72

Issue

3

Publish Date

2011

Start Page

370

End Page

377

DOI

10.1016/j.lungcan.2010.10.011

Disruption of the circadian rhythm or biological clock, which is regulated by a number of clock genes, including circadian locomotor output cycles kaput (CLOCK), period genes (PERs), and cryptochrome genes (CRYs), is a risk factor for breast cancer. We hypothesized that genetic variation in these clock genes may influence breast cancer risk. To test this hypothesis, we designed a hospital-based study that included 1,538 breast cancer patients and 1,605 healthy controls. We genotyped subjects for five single nucleotide polymorphisms (SNPs) and a length variant of the circadian clock genes and evaluated their associations with breast cancer risk. These polymorphisms were determined by TaqMan allelic discrimination assays and the polymerase chain reaction-restriction fragment length polymorphism method. Univariate logistic regression analysis showed that polymorphisms of the CLOCK and CRY1 genes were associated with breast cancer risk. We found that carriers of the CLOCK CT and combined CT+TT genotypes had a significantly higher risk of breast cancer than carriers of the CC genotype (aOR = 1.35, 95% CI = 1.12-1.63 and aOR = 1.30, 95% CI = 1.09-1.56, respectively). Carriers of the CRY1 GT genotype had a decreased risk of breast cancer (aOR = 0.84, 95% CI = 0.71-0.99). We also observed a lower risk of breast cancer in carriers of the CRY2 CC genotype who were ER-positive than in those who were ER-negative (OR = 0.15, 95% CI = 0.04-0.67). When stratified by the CLOCK genotype, patients with the CLOCK CT/ CRY2 CC genotypes had significantly lower cancer risk than those with the GG genotype (aOR = 0.36, 95% CI = 0.14-0.95). Individuals carrying both the CLOCK CC and PER2 AA genotypes had an increased cancer risk (aOR = 2.28, 95% CI = 1.22-4.26). Our study suggests that genetic variants of the circadian rhythm regulatory pathway genes contribute to the differential risk of developing breast cancer in Chinese populations.

Authors

Dai, H; Zhang, L; Cao, M; Song, F; Zheng, H; Zhu, X; Wei, Q; Zhang, W; Chen, K

MLA Citation

Dai, H, Zhang, L, Cao, M, Song, F, Zheng, H, Zhu, X, Wei, Q, Zhang, W, and Chen, K. "The role of polymorphisms in circadian pathway genes in breast tumorigenesis." Breast cancer research and treatment 127.2 (June 2011): 531-540.

PMID

20978934

Source

epmc

Published In

Breast Cancer Research and Treatment

Volume

127

Issue

2

Publish Date

2011

Start Page

531

End Page

540

DOI

10.1007/s10549-010-1231-2

To the best of our knowledge, no studies to date have evaluated roles of insulin-like growth factor binding protein 5 (IGFBP5) polymorphisms in risk of squamous cell carcinoma of the head and neck (SCCHN).A hospital-based study of 1082 patients with SCCHN and 1120 cancer-free controls was performed to investigate associations between 2 functional polymorphisms, -1195T>C and -709G>C, in the IGFBP5 promoter region and SCCHN risk.We demonstrated that the transcription factor, activator protein 1 (AP-1), differentially bound to T or C variants at -1195 in the promoter to regulate the IGFBP5 promoter activity and that the C variant genotypes were associated with deferential risk of late-stage SCCHN, compared to the TT genotype, particularly for human papillomavirus (HPV)-unrelated sites (adjusted odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19-4.11 for CC vs TT).The IGFBP5 -1195T>C polymorphism is functional and may potentially be a biomarker for susceptibility to late-stage SCCHN.

Authors

Niu, J; Huang, Y-J; Wei, S; Liu, Z; Wang, L-E; Chang, S; Chamberlain, RM; El-Naggar, AK; Sturgis, EM; Wei, Q

MLA Citation

Niu, J, Huang, Y-J, Wei, S, Liu, Z, Wang, L-E, Chang, S, Chamberlain, RM, El-Naggar, AK, Sturgis, EM, and Wei, Q. "Association between a functional polymorphism (-1195T>C) in the IGFBP5 promoter and head and neck cancer risk." Head & neck 33.5 (May 2011): 650-660.

PMID

20949447

Source

epmc

Published In

Head & Neck: Journal for the Sciences & Specialties of the Head and Neck

Volume

33

Issue

5

Publish Date

2011

Start Page

650

End Page

660

DOI

10.1002/hed.21514

Platinum-based chemotherapy is the most common treatment for non-small cell lung cancer (NSCLC), and expression levels of drug metabolism and transport proteins are correlated with its efficacy and toxicity. In this study, we investigated the association of three putative functional polymorphisms of ABCC2 (C-24T, G1249A, and C3972T) with tumor response and occurrence of the grade 3 or 4 toxicity in 445 patients with stage III and IV NSCLC treated with platinum-based chemotherapy. We determined the genotypes of these three polymorphisms by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MassArray) method. We found that the common homozygotes of -24C was associated with a better treatment response (adjusted odds ratios [ORs], 1.84; 95% confidence interval [CI], 1.05-3.23; P=0.032). Furthermore, patients with 3972T had increased risk of severe thrombocytopenia toxicity (adjusted OR, 2.43; 95% CI, 1.06-5.56; P=0.034); and in female subgroup analyses, this variant was associated with significantly increased risk of overall toxicity (adjusted OR, 2.63; 95% CI, 1.17-5.95; P=0.02), particularly of hematologic toxicity (adjusted OR, 3.80; 95% CI, 1.62-8.87; P=0.002). Moreover, -24T/3972T haplotype was also associated with significantly increased risk of hematologic toxicity. Our results suggested that C-24T variants had an effect on treatment response and that C3972T had an effect on severe toxicities among platinum-treated non-small cell lung cancer patients.

Authors

Han, B; Gao, G; Wu, W; Gao, Z; Zhao, X; Li, L; Qiao, R; Chen, H; Wei, Q; Wu, J; Lu, D

MLA Citation

Han, B, Gao, G, Wu, W, Gao, Z, Zhao, X, Li, L, Qiao, R, Chen, H, Wei, Q, Wu, J, and Lu, D. "Association of ABCC2 polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients." Lung cancer (Amsterdam, Netherlands) 72.2 (May 2011): 238-243.

PMID

20943283

Source

epmc

Published In

Lung Cancer

Volume

72

Issue

2

Publish Date

2011

Start Page

238

End Page

243

DOI

10.1016/j.lungcan.2010.09.001

Published genome-wide association studies (GWASs) have identified few variants in the known biological pathways involved in lung cancer etiology. To mine the possibly hidden causal single nucleotide polymorphisms (SNPs), we explored all SNPs in the extrinsic apoptosis pathway from our published GWAS dataset for 1154 lung cancer cases and 1137 cancer-free controls. In an initial association analysis of 611 tagSNPs in 41 apoptosis-related genes, we identified only 10 tagSNPs associated with lung cancer risk with a P value<10(-2), including four tagSNPs in DAPK1 and three tagSNPs in TNFSF8. Unlike DAPK1 SNPs, TNFSF8 rs2181033 tagged other four predicted functional but untyped SNPs (rs776576, rs776577, rs31813148 and rs2075533) in the promoter region. Therefore, we further tested binding affinity of these four SNPs by performing the electrophoretic mobility shift assay. We found that only rs2075533T allele modified levels of nuclear proteins bound to DNA, leading to significantly decreased expression of luciferase reporter constructs by 5- to -10-fold in H1299, HeLa and HCT116 cell lines compared with the C allele. We also performed a replication study of the untyped rs2075533 in an independent Texas population but did not confirm the protective effect. We further performed a mini meta-analysis for SNPs of TNFSF8 obtained from other four published lung cancer GWASs with 12  214 cases and 47  721 controls, and we found that only rs3181366 (r2=0.69 with the untyped rs2075533) was associated to lung cancer risk (P=0.008). Our findings suggest a possible role of novel TNFSF8 variants in susceptibility to lung cancer.

Authors

Wei, S; Niu, J; Zhao, H; Liu, Z; Wang, L-E; Han, Y; Chen, WV; Amos, CI; Rafnar, T; Sulem, P; Stefansson, K; Landi, MT; Caporaso, NE; Albanes, D; Thun, MJ; McKay, JD; Brennan, P; Wang, Y; Houlston, RS; Spitz, MR; Wei, Q

MLA Citation

Wei, S, Niu, J, Zhao, H, Liu, Z, Wang, L-E, Han, Y, Chen, WV, Amos, CI, Rafnar, T, Sulem, P, Stefansson, K, Landi, MT, Caporaso, NE, Albanes, D, Thun, MJ, McKay, JD, Brennan, P, Wang, Y, Houlston, RS, Spitz, MR, and Wei, Q. "Association of a novel functional promoter variant (rs2075533 C>T) in the apoptosis gene TNFSF8 with risk of lung cancer--a finding from Texas lung cancer genome-wide association study." Carcinogenesis 32.4 (April 2011): 507-515.

PMID

21292647

Source

epmc

Published In

Carcinogenesis

Volume

32

Issue

4

Publish Date

2011

Start Page

507

End Page

515

DOI

10.1093/carcin/bgr014

Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35).In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies.rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 × 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 × 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86).This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers.Further research is warranted to elucidate the mechanisms underlying these observations.

Authors

Chen, D; Truong, T; Gaborieau, V; Byrnes, G; Chabrier, A; Chuang, S-C; Olshan, AF; Weissler, MC; Luo, J; Romkes, M; Buch, S; Nukui, T; Franceschi, S; Herrero, R; Talamini, R; Kelsey, KT; Christensen, B; McClean, MD; Lacko, M; Manni, JJ; Peters, WHM; Lubiński, J; Trubicka, J; Lener, M; Muscat, JE; Lazarus, P; Wei, Q; Sturgis, EM; Zhang, Z-F; Chang, S-C; Wang, R; Schwartz, SM; Chen, C; Benhamou, S; Lagiou, P; Holcátová, I; Richiardi, L; Kjaerheim, K; Agudo, A; Castellsagué, X; Macfarlane, TV et al.

MLA Citation

Chen, D, Truong, T, Gaborieau, V, Byrnes, G, Chabrier, A, Chuang, S-C, Olshan, AF, Weissler, MC, Luo, J, Romkes, M, Buch, S, Nukui, T, Franceschi, S, Herrero, R, Talamini, R, Kelsey, KT, Christensen, B, McClean, MD, Lacko, M, Manni, JJ, Peters, WHM, Lubiński, J, Trubicka, J, Lener, M, Muscat, JE, Lazarus, P, Wei, Q, Sturgis, EM, Zhang, Z-F, Chang, S-C, Wang, R, Schwartz, SM, Chen, C, Benhamou, S, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, and Macfarlane, TV et al. "A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20.4 (April 2011): 658-664.

PMID

21335511

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

20

Issue

4

Publish Date

2011

Start Page

658

End Page

664

DOI

10.1158/1055-9965.epi-10-1008

DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1154 lung cancer cases and 1137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P-value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test=4.89 x 10⁻⁴). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test=1.3 x 10⁻³). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR=0.80, 95% CI=0.62-1.03 and P=0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR=0.77, 95% CI=0.66-0.89, P(dominant)=5 x 10⁻⁴ and P for trend=5 x 10⁻⁴) and rs1478486 (adjusted OR=0.82, 95% CI=0.71-0.94, P(dominant)=6 x 10⁻³ and P for trend=3.5 x 10⁻³). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.

Authors

Yu, H; Zhao, H; Wang, L-E; Han, Y; Chen, WV; Amos, CI; Rafnar, T; Sulem, P; Stefansson, K; Landi, MT; Caporaso, N; Albanes, D; Thun, M; McKay, JD; Brennan, P; Wang, Y; Houlston, RS; Spitz, MR; Wei, Q

MLA Citation

Yu, H, Zhao, H, Wang, L-E, Han, Y, Chen, WV, Amos, CI, Rafnar, T, Sulem, P, Stefansson, K, Landi, MT, Caporaso, N, Albanes, D, Thun, M, McKay, JD, Brennan, P, Wang, Y, Houlston, RS, Spitz, MR, and Wei, Q. "An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs." DNA repair 10.4 (April 2011): 398-407.

PMID

21296624

Source

epmc

Published In

DNA Repair

Volume

10

Issue

4

Publish Date

2011

Start Page

398

End Page

407

DOI

10.1016/j.dnarep.2011.01.005

P21 (CDKN1A), a key cell cycle regulatory protein that governs cell cycle progression from G1 to S phase, can regulate cell proliferation, growth arrest, and apoptosis. The Ser31Arg polymorphism is located in the highly conserved region of p21 and may encode functionally distinct proteins. Although many epidemiological studies have been conducted to evaluate the association between the p21 Ser31Arg polymorphism and cancer risk, the findings remain conflicting. This meta-analysis with 33 077 cases and 45 013 controls from 44 published case-control studies showed that the variant homozygous 31Arg/Arg genotype was associated with an increased risk of numerous types of cancers in a random-effect model (homozygote comparison: OR = 1.17, 95% CI = 0.99 to 1.37, P = 0.0002 for the heterogeneity test; recessive model comparison: OR = 1.16, 95% CI = 1.01 to 1.33, P = 0.0001 for the heterogeneity test). Stratified analysis revealed that increased cancer risk associated with the 31Arg/Arg genotype remained significant in subgroups of colorectal cancer, estrogen-related cancer, Caucasians, population-based studies, studies with matching information or a larger sample size. Heterogeneity analysis showed that tumor type contributed to substantial between-study heterogeneity (recessive model comparison: Χ(2) = 21.83, df = 7, P = 0.003). The results from this large-sample sized meta-analysis suggest that the p21 31Arg/Arg genotype may serve as a potential marker for increased cancer risk.

Authors

Ma, H; Zhou, Z; Wei, S; Wei, Q

MLA Citation

Ma, H, Zhou, Z, Wei, S, and Wei, Q. "Association between p21 Ser31Arg polymorphism and cancer risk: a meta-analysis." Chinese journal of cancer 30.4 (April 2011): 254-263.

PMID

21439247

Source

epmc

Published In

Ai zheng = Aizheng = Chinese journal of cancer

Volume

30

Issue

4

Publish Date

2011

Start Page

254

End Page

263

Two genome-wide association studies of glioma in European populations identified 14 genetic variants strongly associated with risk of glioma, but it is unknown whether these variants are associated with glioma risk in Asian populations. The authors genotyped these 14 variants in 976 glioma patients and 1,057 control subjects to evaluate their associations with risk of glioma, particularly high-grade glioma (glioblastoma; n = 312), in a Chinese population (2004-2009). Overall, the authors identified 3 susceptibility loci for glioma risk at 20q13.33 (RTEL1 rs6010620 (P = 2.79 × 10(-6))), 11q23.3 (PHLDB1 rs498872 (P = 3.8 × 10(-6))), and 5p15.33 (TERT rs2736100 (P = 3.69 × 10(-4))) in this study population; these loci were also associated with glioblastoma risk (20q13.33: RTEL1 rs6010620 (P = 3.57 × 10(-7)); 11q23.3: PHLDB1 rs498872 (P = 7.24 × 10(-3)); 5p15.33: TERT rs2736100 and TERT rs2736098 (P = 1.21 × 10(-4) and P = 2.84 × 10(-4), respectively)). This study provides further evidence for 3 glioma susceptibility regions at 20q13.33, 11q23.3, and 5p15.33 in Chinese populations.

Authors

Chen, H; Chen, Y; Zhao, Y; Fan, W; Zhou, K; Liu, Y; Zhou, L; Mao, Y; Wei, Q; Xu, J; Lu, D

MLA Citation

Chen, H, Chen, Y, Zhao, Y, Fan, W, Zhou, K, Liu, Y, Zhou, L, Mao, Y, Wei, Q, Xu, J, and Lu, D. "Association of sequence variants on chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) with glioma susceptibility in a Chinese population." American journal of epidemiology 173.8 (April 2011): 915-922.

PMID

21350045

Source

epmc

Published In

American Journal of Epidemiology

Volume

173

Issue

8

Publish Date

2011

Start Page

915

End Page

922

DOI

10.1093/aje/kwq457

IQGAP1 knockout mice develop gastric cancer, but the IQGAP1 protein is associated with some advanced-stage human cancers. IQGAP1 expression is regulated by a microRNA, miR-124, through a binding site at the 3'-untranslated region, where a single nucleotide polymorphism (SNP) exists in the core binding region. We asked whether IQGAP1 expression is associated with breast cancer development and whether genetic variants at the miR-124 binding site are important. We genotyped the IQGAP1 SNP rs1042538 A/T in 1,541 breast cancer cases and 1,598 controls and analyzed the frequency of the variant and interactions with major risk factors in these populations. We also measured the expression of IQGAP1 at both mRNA and protein levels in different IQGAP1 genotypes. The IQGAP1 TT genotype, compared with the AA genotype, was associated with a significantly lower risk of developing breast cancer [P=0.049, odds ratio (OR), 0.78; 95% confidence interval (CI), 0.61-0.99]. In case-only analyses, the TT, compared with the AA, genotype was associated with progesterone receptor-positive subjects (OR, 1.35; 95% CI, 1.00-1.83). The expression levels of IQGAP1 protein were significantly higher in the TT genotype compated to the AA genotype. The presence of SNPs at the miR-124 binding site may be a marker for predicting breast cancer risk and prognosis.

Authors

Zheng, H; Song, F; Zhang, L; Yang, D; Ji, P; Wang, Y; Almeida, M; Calin, GA; Hao, X; Wei, Q; Zhang, W; Chen, K

MLA Citation

Zheng, H, Song, F, Zhang, L, Yang, D, Ji, P, Wang, Y, Almeida, M, Calin, GA, Hao, X, Wei, Q, Zhang, W, and Chen, K. "Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer." International journal of oncology 38.4 (April 2011): 1153-1161.

PMID

21318219

Source

epmc

Published In

International journal of oncology

Volume

38

Issue

4

Publish Date

2011

Start Page

1153

End Page

1161

DOI

10.3892/ijo.2011.940

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Authors

McKay, JD; Truong, T; Gaborieau, V; Chabrier, A; Chuang, S-C; Byrnes, G; Zaridze, D; Shangina, O; Szeszenia-Dabrowska, N; Lissowska, J; Rudnai, P; Fabianova, E; Bucur, A; Bencko, V; Holcatova, I; Janout, V; Foretova, L; Lagiou, P; Trichopoulos, D; Benhamou, S; Bouchardy, C; Ahrens, W; Merletti, F; Richiardi, L; Talamini, R; Barzan, L; Kjaerheim, K; Macfarlane, GJ; Macfarlane, TV; Simonato, L; Canova, C; Agudo, A; Castellsagué, X; Lowry, R; Conway, DI; McKinney, PA; Healy, CM; Toner, ME et al.

MLA Citation

McKay, JD, Truong, T, Gaborieau, V, Chabrier, A, Chuang, S-C, Byrnes, G, Zaridze, D, Shangina, O, Szeszenia-Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Holcatova, I, Janout, V, Foretova, L, Lagiou, P, Trichopoulos, D, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, GJ, Macfarlane, TV, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, DI, McKinney, PA, Healy, CM, and Toner, ME et al. "A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium." PLoS genetics 7.3 (March 17, 2011): e1001333-.

PMID

21437268

Source

epmc

Published In

PLoS genetics

Volume

7

Issue

3

Publish Date

2011

Start Page

e1001333

DOI

10.1371/journal.pgen.1001333

Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.In 17 previously published studies, 1,787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR; i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated OR or HR with 95% CIs to estimate the risk or hazard.We found consistent and clinically substantial risk or hazard for TR, PFS, and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response and poor PFS and OS in Asians (TR: OR = 0.53 and 95% CI = 0.35-0.81; PFS: HR = 1.69 and 95% CI = 1.05-2.70; and OS: HR = 2.03 and 95% CI = 1.60-2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response and poor PFS and OS in Caucasians (TR: OR = 0.56 and 95% CI = 0.35-0.88; PFS: HR = 1.41 and 95% CI = 1.02-1.95; and OS: HR = 1.42 and 95% CI = 1.11-1.81).NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin-based treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings.

Authors

Yin, M; Yan, J; Martinez-Balibrea, E; Graziano, F; Lenz, H-J; Kim, H-J; Robert, J; Im, S-A; Wang, W-S; Etienne-Grimaldi, M-C; Wei, Q

MLA Citation

Yin, M, Yan, J, Martinez-Balibrea, E, Graziano, F, Lenz, H-J, Kim, H-J, Robert, J, Im, S-A, Wang, W-S, Etienne-Grimaldi, M-C, and Wei, Q. "ERCC1 and ERCC2 polymorphisms predict clinical outcomes of oxaliplatin-based chemotherapies in gastric and colorectal cancer: a systemic review and meta-analysis." Clinical cancer research : an official journal of the American Association for Cancer Research 17.6 (March 2011): 1632-1640. (Review)

PMID

21278243

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

17

Issue

6

Publish Date

2011

Start Page

1632

End Page

1640

DOI

10.1158/1078-0432.ccr-10-2169

p14(ARF) , an alternate reading frame (ARF) product of the cyclin-dependent kinase inhibitor 2A locus, plays a critical role in crosstalk between the tumor protein 53 (p53) and retinoblastoma (Rb) pathways and in cellular anticancer mechanisms. Therefore, the authors of this report investigated the association between single nucleotide polymorphisms (SNPs) of the p14(ARF) gene and the risk of developing a second primary malignancy (SPM) after an index squamous cell carcinoma of the head and neck (SCCHN).The log-rank test and Cox proportional hazards models were used to assess the association of 2 p14(ARF) SNPs (reference SNP [rs]3731217 and rs3088440) with SPM-free survival and with the risk of developing an SPM among 1287 patients who had SCCHN.Patients with either p14(ARF) variant genotypes of the 2 polymorphisms had a significantly reduced SPM-free survival compared with patients with no variant genotypes (log-rank test; P = .006). Compared with the p14(ARF) thymine-thymine (TT) and guanine-guanine (GG) genotypes, the variant genotypes of p14(ARF) TG/GG and guanine-adenine (GA)/AA were associated with a significantly moderately increased risk of developing an SPM (p14(ARF) rs3731217: adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.00-2.19; p14(ARF) rs3088440: aHR, 1.61; 95% CI, 1.07-2.43). Moreover, after combining the variant genotypes of the 2 SNPs, patients who had variant genotypes were at significantly greater risk of developing an SPM compared with patients who had no variant genotypes (aHR, 3.07; 95% CI, 1.54-6.12), and the risk was particularly pronounced in several subgroups.The current results suggested that there is a modestly increased risk of developing an SPM after an index SCCHN with each p14(ARF) polymorphism, and there is an even greater risk of developing an SPM for patients with combined variant genotypes of the 2 SNPs. Therefore, p14(ARF) polymorphisms may be susceptible markers of the risk of developing an SPM in patients with SCCHN.

Authors

Zhang, Y; Sturgis, EM; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Zhang, Y, Sturgis, EM, Zafereo, ME, Wei, Q, and Li, G. "p14ARF genetic polymorphisms and susceptibility to second primary malignancy in patients with index squamous cell carcinoma of the head and neck." Cancer 117.6 (March 2011): 1227-1235.

PMID

21381012

Source

epmc

Published In

Cancer

Volume

117

Issue

6

Publish Date

2011

Start Page

1227

End Page

1235

DOI

10.1002/cncr.25605

SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. SULF1 expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics.We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method.We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (P = 0.027; Ptrend = 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (P = 0.013; Ptrend= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (P = 0.014; Ptrend = 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line.These findings suggest that genetic variations in SULF1 may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of SULF1 SNPs are warranted.

Authors

Han, CH; Huang, Y-J; Lu, KH; Liu, Z; Mills, GB; Wei, Q; Wang, L-E

MLA Citation

Han, CH, Huang, Y-J, Lu, KH, Liu, Z, Mills, GB, Wei, Q, and Wang, L-E. "Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer." Journal of experimental & clinical cancer research : CR 30 (January 7, 2011): 5-.

PMID

21214932

Source

epmc

Published In

Journal of Experimental and Clinical Cancer Research

Volume

30

Publish Date

2011

Start Page

5

DOI

10.1186/1756-9966-30-5

The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.

Authors

Yin, M; Liao, Z; Huang, Y-J; Liu, Z; Yuan, X; Gomez, D; Wang, L-E; Wei, Q

MLA Citation

Yin, M, Liao, Z, Huang, Y-J, Liu, Z, Yuan, X, Gomez, D, Wang, L-E, and Wei, Q. "Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy." PloS one 6.5 (January 2011): e20055-.

PMID

21647442

Source

epmc

Published In

PloS one

Volume

6

Issue

5

Publish Date

2011

Start Page

e20055

DOI

10.1371/journal.pone.0020055

Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting.A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ(2)-based Q statistic test and Egger's test, respectively.The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14-1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38-2.44), lung cancer (OR = 2.39, 95% CI = 1.18-4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83-2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53-1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12-2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis (P = 0.532).The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.

Authors

Ma, H; Zhou, Z; Wei, S; Liu, Z; Pooley, KA; Dunning, AM; Svenson, U; Roos, G; Hosgood, HD; Shen, M; Wei, Q

MLA Citation

Ma, H, Zhou, Z, Wei, S, Liu, Z, Pooley, KA, Dunning, AM, Svenson, U, Roos, G, Hosgood, HD, Shen, M, and Wei, Q. "Shortened telomere length is associated with increased risk of cancer: a meta-analysis." PloS one 6.6 (January 2011): e20466-.

PMID

21695195

Source

epmc

Published In

PloS one

Volume

6

Issue

6

Publish Date

2011

Start Page

e20466

DOI

10.1371/journal.pone.0020466

BACKGROUND: The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes. METHODS: The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations. RESULTS: The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014. CONCLUSIONS: Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.

Authors

Zhou, K; Hu, D; Lu, J; Fan, W; Liu, H; Chen, H; Chen, G; Wei, Q; Du, G; Mao, Y; Lu, D; Zhou, L

MLA Citation

Zhou, K, Hu, D, Lu, J, Fan, W, Liu, H, Chen, H, Chen, G, Wei, Q, Du, G, Mao, Y, Lu, D, and Zhou, L. "A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population." BMC cancer 11 (January 2011): 104-.

PMID

21429202

Source

epmc

Published In

BMC Cancer

Volume

11

Publish Date

2011

Start Page

104

DOI

10.1186/1471-2407-11-104

NRAS and BRAF mutations are common in cutaneous melanomas, although rarely detected mutually in the same tumor. Distinct clinical correlates of these mutations have not been described, despite in vitro data suggesting enhanced oncogenic effects. This study was designed to test the hypothesis that primary human cutaneous melanomas harboring mutations in NRAS or BRAF display a more aggressive clinical phenotype than tumors wild type at both loci.Microdissection of 223 primary melanomas was carried out, followed by determination of the NRAS and BRAF mutational status. Genotypic findings were correlated with features known to influence tumor behavior including age, gender, Breslow depth, Clark level, mitotic rate, the presence of ulceration, and American Joint Committee on Cancer (AJCC) staging.Breslow depth and Clark level varied significantly among the genotypes, with NRAS mutants showing the deepest levels and wild-type tumors the least depth. Ulceration also differed significantly among the genotypes, with BRAF mutants demonstrating the highest rate. In addition, tumors with mutated NRAS were more likely to be located on the extremities. Patients whose tumors carried either mutation presented with more advanced AJCC stages compared with patients with wild-type tumors, and specifically, were more likely to have stage III disease at diagnosis. Overall survival did not differ among the 3 groups.Distinct clinical phenotypes exist for melanomas bearing NRAS and BRAF mutations, whether considered together or separately, and are associated with features known to predict aggressive tumor behavior. The impact of these mutations is most evident at earlier stages of disease progression.

Authors

Ellerhorst, JA; Greene, VR; Ekmekcioglu, S; Warneke, CL; Johnson, MM; Cooke, CP; Wang, L-E; Prieto, VG; Gershenwald, JE; Wei, Q; Grimm, EA

MLA Citation

Ellerhorst, JA, Greene, VR, Ekmekcioglu, S, Warneke, CL, Johnson, MM, Cooke, CP, Wang, L-E, Prieto, VG, Gershenwald, JE, Wei, Q, and Grimm, EA. "Clinical correlates of NRAS and BRAF mutations in primary human melanoma." Clinical cancer research : an official journal of the American Association for Cancer Research 17.2 (January 2011): 229-235.

PMID

20975100

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

17

Issue

2

Publish Date

2011

Start Page

229

End Page

235

DOI

10.1158/1078-0432.ccr-10-2276

Matrix metallopeptidase 1 (MMP1) is one of the interstitial collagens in the extracellular matrix metalloproteinase family and involved in tumour behaviours. However, there is no report on the role of genetic variation in MMP1 in risk of cutaneous melanoma (CM). We investigated the association between genotypes and haplotypes of seven reported MMP1 promoter polymorphisms [-1607G ins/del (2G/1G), -839G>A, -755T>G, -519A>G, -422A>T, -340A>G and -320T>C, genotyped by the TaqMan assay] and CM risk in 872 patients and 873 cancer-free controls. These seven polymorphisms were not in linkage disequilibrium among each other (r(2)<0.63). Compared to their common homozygous genotypes, the variant -519GG was associated with significantly decreased CM risk [adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.52-0.99], whereas variants -422TT and -320CC were associated with significantly increased CM risk (OR=1.50, 95% CI=1.11-2.03 and OR=1.72, 95% CI=1.05-2.81, respectively) after adjustment for age, sex, family history and sun-exposure-related risk factors. The number of risk alleles of these three polymorphisms was associated with CM risk in a dose-response manner (P(trend)=0.0002). In the stratification analysis, we found that the associations of these polymorphisms with CM risk were modified by some of the risk factors. Furthermore, the haplotypes Gdel-A-G-A-T-G-T and G-G-G-A-T-A-T were associated with significantly increased CM risk (ORs=1.56 and 2.13, 95% CIs=1.02-2.38 and 1.22-3.70, respectively). These findings suggest that MMP1 promoter polymorphisms may individually or jointly play roles in the development of CM.

Authors

Wang, L-E; Huang, Y-J; Yin, M; Gershenwald, JE; Prieto, VG; Lee, JE; Duvic, M; Grimm, EA; Wei, Q

MLA Citation

Wang, L-E, Huang, Y-J, Yin, M, Gershenwald, JE, Prieto, VG, Lee, JE, Duvic, M, Grimm, EA, and Wei, Q. "Promoter polymorphisms in matrix metallopeptidase 1 and risk of cutaneous melanoma." European journal of cancer (Oxford, England : 1990) 47.1 (January 2011): 107-115.

PMID

20655738

Source

epmc

Published In

European Journal of Cancer

Volume

47

Issue

1

Publish Date

2011

Start Page

107

End Page

115

DOI

10.1016/j.ejca.2010.06.129

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.

Authors

Sigurdson, AJ; Jones, IM; Wei, Q; Wu, X; Spitz, MR; Stram, DA; Gross, MD; Huang, W-Y; Wang, L-E; Gu, J; Thomas, CB; Reding, DJ; Hayes, RB; Caporaso, NE

MLA Citation

Sigurdson, AJ, Jones, IM, Wei, Q, Wu, X, Spitz, MR, Stram, DA, Gross, MD, Huang, W-Y, Wang, L-E, Gu, J, Thomas, CB, Reding, DJ, Hayes, RB, and Caporaso, NE. "Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial." Carcinogenesis 32.1 (January 2011): 69-73.

PMID

20929901

Source

epmc

Published In

Carcinogenesis

Volume

32

Issue

1

Publish Date

2011

Start Page

69

End Page

73

DOI

10.1093/carcin/bgq204

Authors

Doan, PC; Sturgis, EM; Wei, Q; Li, G

MLA Citation

Doan, PC, Sturgis, EM, Wei, Q, and Li, G. "Association of BRCA1 Single Nucleotide Polymorphisms with Risk of Differentiated Thyroid Carcinoma." The Laryngoscope 121.S4 (2011): S110-S110.

Source

crossref

Published In

The Laryngoscope

Volume

121

Issue

S4

Publish Date

2011

Start Page

S110

End Page

S110

DOI

10.1002/lary.21987

Authors

Chuang, S-C; Agudo, A; Ahrens, W; Anantharaman, D; Benhamou, S; Boccia, S; Chen, C; Conway, DI; Fabianova, E; Hayes, RB; Healy, CM; Holcatova, I; Kjaerheim, K; Lagiou, P; Lazarus, P; Macfarlane, TV; Mahimkar, MB; Mates, D; Matsuo, K; Merletti, F; Metspalu, A; Morgenstern, H; Muscat, J; Cadoni, G; Olshan, AF; Purdue, M; Ramroth, H; Rudnai, P; Schwartz, SM; Simonato, L; Smith, EM; Sturgis, EM; Szeszenia-Dabrowska, N; Talamini, R; Thomson, P; Wei, Q; Zaridze, D; Zhang, Z-F; Znaor, A; Brennan, P et al.

MLA Citation

Chuang, S-C, Agudo, A, Ahrens, W, Anantharaman, D, Benhamou, S, Boccia, S, Chen, C, Conway, DI, Fabianova, E, Hayes, RB, Healy, CM, Holcatova, I, Kjaerheim, K, Lagiou, P, Lazarus, P, Macfarlane, TV, Mahimkar, MB, Mates, D, Matsuo, K, Merletti, F, Metspalu, A, Morgenstern, H, Muscat, J, Cadoni, G, Olshan, AF, Purdue, M, Ramroth, H, Rudnai, P, Schwartz, SM, Simonato, L, Smith, EM, Sturgis, EM, Szeszenia-Dabrowska, N, Talamini, R, Thomson, P, Wei, Q, Zaridze, D, Zhang, Z-F, Znaor, A, and Brennan, P et al. "Sequence Variants and the Risk of Head and Neck Cancer: Pooled Analysis in the INHANCE Consortium." Frontiers in Oncology 1 (2011).

Source

crossref

Published In

Frontiers in Oncology

Volume

1

Publish Date

2011

DOI

10.3389/fonc.2011.00013

Human DEC1 (deleted in esophageal cancer 1) gene is located on chromosome 9q, a region frequently deleted in various types of human cancers, including squamous cell carcinoma of the head and neck (SCCHN). However, only one epidemiological study has evaluated the association between DEC1 polymorphisms and cancer risk. In this hospital-based case-control study, four potentially functional single-nucleotide polymorphisms -1628 G>A (rs1591420), -606 T>C [rs4978620, in complete linkage disequilibrium with -249T>C (rs2012775) and -122 G>A(rs2012566)], c.179 C>T p.Ala60Val (rs2269700) and 3' untranslated region-rs3750505 as well as the TP53 tumor suppressor gene codon 72 (Arg72Pro, rs1042522) polymorphism were genotyped in 1111 non-Hispanic Whites SCCHN patients and 1130 age-and sex-matched cancer-free controls. After adjustment for age, sex and smoking and drinking status, the variant -606CC (i.e. -249CC) homozygotes had a significantly reduced SCCHN risk (adjusted odds ratio = 0.71, 95% confidence interval = 0.52-0.99) compared with the -606TT homozygotes. Stratification analyses showed that a reduced risk associated with the -606CC genotype was more pronounced in subgroups of non-smokers, non-drinkers, younger subjects (defined as ≤57 years), carriers of the TP53 Arg/Arg (rs1042522) genotype, patients with oropharyngeal cancer or late-stage SCCHN. Further in silico analysis revealed that the -249 T-to-C change led to a gain of a transcription factor-binding site. Additional functional analysis showed that the -249T-to-C change significantly enhanced transcriptional activity of the DEC1 promoter and the DNA-protein-binding activity. We conclude that the DEC1 promoter -249 T>C (rs2012775) polymorphism is functional, modulating susceptibility to SCCHN among non-Hispanic Whites.

Authors

Huang, Y-J; Niu, J; Wei, S; Yin, M; Liu, Z; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Huang, Y-J, Niu, J, Wei, S, Yin, M, Liu, Z, Wang, L-E, Sturgis, EM, and Wei, Q. "A novel functional DEC1 promoter polymorphism -249T>C reduces risk of squamous cell carcinoma of the head and neck." Carcinogenesis 31.12 (December 2010): 2082-2090.

PMID

20935061

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

12

Publish Date

2010

Start Page

2082

End Page

2090

DOI

10.1093/carcin/bgq198

Single-nucleotide polymorphisms (SNPs) of TERT-rs2736098 (C > T) and CLPTM1L-rs401681(C > T) at the 5p15.33 locus are significantly associated with cancer risk as reported in genome-wide association studies (GWAS), but there are no reported studies for squamous cell carcinoma of the head and neck (SCCHN). In a case-control study of 1079 SCCHN cases and 1115 cancer-free controls of non-Hispanic whites who were frequency matched by age and sex, we genotyped for these two SNPs and assessed their associations with SCCHN risk. Compared with the CC genotypes of each polymorphism, the associations of a slightly reduced risk of SCCHN with the variant genotypes of CT + TT of both polymorphisms were approaching statistical significance [Odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.76-1.08 for TERT-rs2736098 and OR = 0.86, 95% CI = 0.71-1.04 for CLPTM1L-rs401681, respectively]. When the two SNPs were combined, the variant genotypes of the two SNPs were significantly associated a moderately reduced risk of SCCHN (OR = 0.82, 95% CI = 0.67-0.99), and the number of variant genotypes was associated with a significantly reduced risk in a dose-response manner (P = 0.028). Furthermore, the reduced risk was more pronounced in ever smokers, ever drinkers and patients with oropharyngeal cancer. Our results suggested that these two SNPs at the 5p15.33 locus may be associated with a reduced risk of SCCHN, particularly for their combined effect. Although we added additional evidence for the association of the two SNPs with cancer risk as reported in GWAS, additional studies are needed to replicate our findings.

Authors

Liu, Z; Li, G; Wei, S; Niu, J; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Li, G, Wei, S, Niu, J, Wang, L-E, Sturgis, EM, and Wei, Q. "Genetic variations in TERT-CLPTM1L genes and risk of squamous cell carcinoma of the head and neck." Carcinogenesis 31.11 (November 2010): 1977-1981.

PMID

20802237

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

11

Publish Date

2010

Start Page

1977

End Page

1981

DOI

10.1093/carcin/bgq179

The incidence of nonmelanoma skin cancer (NMSC) is equivalent to that of all other cancers combined. Previously, we mapped the 12-O-tetradecanoylphorbol-13-acetate (TPA) skin tumor promotion susceptibility locus, Psl1, to distal chromosome 9 in crosses of sensitive DBA/2 mice with relatively resistant C57BL/6 mice. Here, we used the mouse two-stage skin carcinogenesis model to identify the gene(s) responsible for the effects of Psl1.Interval-specific congenic mouse strains (n ≥ 59 mice per strain) were used to more precisely map the Psl1 locus. Having identified glutathione S-transferase α4 (Gsta4) as a candidate tumor promotion susceptibility gene that mapped within the delimited region, we analyzed Gsta4-deficient mice (n = 62) for susceptibility to skin tumor promotion by TPA. We used quantitative polymerase chain reaction, western blotting, and immunohistochemistry to verify induction of Gsta4 in mouse epidermis following TPA treatment and biochemical assays to associate Gsta4 activity with tumor promotion susceptibility. In addition, single-nucleotide polymorphisms (SNPs) in GSTA4 were analyzed in a case-control study of 414 NMSC patients and 450 control subjects to examine their association with human NMSC. Statistical analyses of tumor studies in mice were one-sided, whereas all other statistical analyses were two-sided.Analyses of congenic mice indicated that at least two loci, Psl1.1 and Psl1.2, map to distal chromosome 9 and confer susceptibility to skin tumor promotion by TPA. Gsta4 maps to Psl1.2 and was highly induced (mRNA and protein) in the epidermis of resistant C57BL/6 mice compared with that of sensitive DBA/2 mice following treatment with TPA. Gsta4 activity levels were also higher in the epidermis of C57BL/6 mice following treatment with TPA. Gsta4-deficient mice (C57BL/6.Gsta4(-/-) mice) were more sensitive to TPA skin tumor promotion (0.8 tumors per mouse vs 0.4 tumors per mouse in wild-type controls; difference = 0.4 tumors per mouse; 95% confidence interval = 0.1 to 0.7, P = .007). Furthermore, inheritance of polymorphisms in GSTA4 was associated with risk of human NMSC. Three SNPs were found to be independent predictors of NMSC risk. Two of these were associated with increased risk of NMSC (odds ratios [ORs] = 1.60 to 3.42), while the third was associated with decreased risk of NMSC (OR = 0.63). In addition, a fourth SNP was associated with decreased risk of basal cell carcinoma only (OR = 0.44).Gsta4/GSTA4 is a novel susceptibility gene for NMSC that affects risk in both mice and humans.

Authors

Abel, EL; Angel, JM; Riggs, PK; Langfield, L; Lo, H-H; Person, MD; Awasthi, YC; Wang, L-E; Strom, SS; Wei, Q; DiGiovanni, J

MLA Citation

Abel, EL, Angel, JM, Riggs, PK, Langfield, L, Lo, H-H, Person, MD, Awasthi, YC, Wang, L-E, Strom, SS, Wei, Q, and DiGiovanni, J. "Evidence that Gsta4 modifies susceptibility to skin tumor development in mice and humans." JNCI Journal of the National Cancer Institute 102.21 (November 2010): 1663-1675.

PMID

20966433

Source

epmc

Published In

Journal of the National Cancer Institute

Volume

102

Issue

21

Publish Date

2010

Start Page

1663

End Page

1675

DOI

10.1093/jnci/djq392

BACKGROUND: Glutathione-S-transferase (GST) enzymes play a role in scavenging endogenous oxidants. Altered enzyme activity results from inherited polymorphisms, which results in increased oxidative stress. This study explores the role of GST polymorphisms as modifiers of surgical complications in patients undergoing head and neck microvascular reconstruction. METHODS: Patients newly diagnosed as having head and neck cancer and undergoing microvascular reconstruction were selected. Polymerase chain reaction was used to determine GST genotypes. Demographic factors, treatment, and postoperative complications were reviewed. Multivariate logistic regression analysis was used to estimate the risk of surgical complications associated with variant genotypes. RESULTS: A total of 107 patients were evaluated. Surgical and medical complication rates were 44.9% and 25.2%, respectively. The variant Val allele at the GSTP1 105 codon was associated with a significantly increased risk of surgical complications (P = .046; adjusted relative risk, 1.7; 95% confidence interval, 1.1-2.6). There was no significant association between the other GST variant genotypes and surgical complications. No association was noted between variant GST genotypes and the risk of medical complications. CONCLUSION: GSTP1 codon 105 polymorphism may be a marker for risk of wound complications in head and neck microvascular reconstruction.

Authors

Zevallos, JP; Hanasono, MM; Li, G; Wei, Q; Sturgis, EM

MLA Citation

Zevallos, JP, Hanasono, MM, Li, G, Wei, Q, and Sturgis, EM. "Glutathione-S-transferase polymorphisms and complications of microvascular head and neck reconstruction." Archives of facial plastic surgery 12.6 (November 2010): 373-378.

PMID

21079113

Source

epmc

Published In

Archives of Facial Plastic Surgery

Volume

12

Issue

6

Publish Date

2010

Start Page

373

End Page

378

DOI

10.1001/archfacial.2010.88

It is unknown whether there are survival disparities between men and women with squamous cell carcinoma of the head and neck (SCCHN), although some data suggest that men have worse outcomes. We conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a survival advantage exists for female compared with male SCCHN patients receiving similar care.We selected 286 female patients and 286 matched male patients from within a prospective epidemiologic study on 1,654 patients with incident SCCHN evaluated and treated at a single large multidisciplinary cancer center. Matching variables included age (±10 y), race/ethnicity, smoking status (never versus ever), tumor site (oral cavity versus oropharynx versus larynx versus hypopharynx), tumor classification (T(1-2) versus T(3-4)), nodal status (negative versus positive), and treatment (surgery, radiation therapy, surgery and radiation therapy, surgery and chemotherapy, chemoradiotherapy, or surgery and chemoradiotherapy).Matched-pair and log-rank analyses showed no significant differences between women and men in recurrence-free, disease-specific, or overall survival. When the analysis was restricted to individual sites (oral cavity, oropharynx, or larynx/hypopharynx), there was also no evidence of a disparity in survival associated with sex.We conclude that there is no evidence to suggest that a survival advantage exists for women as compared with men with SCCHN receiving similar multidisciplinary directed care at a tertiary cancer center.

Authors

Roberts, JC; Li, G; Reitzel, LR; Wei, Q; Sturgis, EM

MLA Citation

Roberts, JC, Li, G, Reitzel, LR, Wei, Q, and Sturgis, EM. "No evidence of sex-related survival disparities among head and neck cancer patients receiving similar multidisciplinary care: a matched-pair analysis." Clinical cancer research : an official journal of the American Association for Cancer Research 16.20 (October 13, 2010): 5019-5027.

PMID

20943762

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

16

Issue

20

Publish Date

2010

Start Page

5019

End Page

5027

DOI

10.1158/1078-0432.ccr-10-0755

Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) may alter the processing, transcription, and expression of miRNAs and, thus, may contribute to cancer development. The authors hypothesized that common polymorphisms in pre-miRNAs are associated individually and (more likely) collectively with the risk of squamous cell carcinoma of the head and neck (SCCHN).The authors genotyped 4 common polymorphisms in pre-miRNAs: Homo sapiens miRNA 146a (hsa-mir-146a) (reference SNP 2910164 [rs2910164]; guanine to cytosine [G→C]), hsa-mir-149 (rs2292832; guanine to thymine [G→T]), hsa-mir-196a2 (rs11614913; C→T), and hsa-mir-499 (rs3746444; adenine to guanine [A→G]) in 1109 patients with SCCHN (cases) and in 1130 cancer-free patients (controls) in a non-Hispanic white population that was frequency-matched by age and sex. Univariate and multivariate logistic regression models were used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Of the 4 SNPs that were studied, the hsa-mir-499 AG and GG genotypes were associated with a reduced risk of SCCHN (OR, 0.83; 95% CI, 0.69-0.99). When the 4 SNPs were combined according to putative risk genotype, the number of observed risk genotypes was associated with an increased risk of SCCHN in a dose-response manner with ORs of 1.0, 1.20, and 1.40 for individuals who had 0 or 1 risk genotypes, 2 or 3 risk genotypes, and 4 risk genotypes, respectively (P(trend) = .037). Specifically, the risk was 1.23-fold (95% CI, 0.98-fold to 1.56-fold) for individuals with 2 to 4 risk genotypes and 1.40-fold (95% CI, 1.02-fold to 1.92-fold) for individuals who had 4 risk genotypes compared with individuals who had 0 or 1 risk genotypes. This risk was more pronounced in men and in patients with oropharyngeal cancer.The combined risk genotypes of 4 common SNPs in pre-miRNAs were associated significantly with a moderately increased risk of SCCHN. Larger studies are needed to validate the current findings.

Authors

Liu, Z; Li, G; Wei, S; Niu, J; El-Naggar, AK; Sturgis, EM; Wei, Q

MLA Citation

Liu, Z, Li, G, Wei, S, Niu, J, El-Naggar, AK, Sturgis, EM, and Wei, Q. "Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck." Cancer 116.20 (October 2010): 4753-4760.

PMID

20549817

Source

epmc

Published In

Cancer

Volume

116

Issue

20

Publish Date

2010

Start Page

4753

End Page

4760

DOI

10.1002/cncr.25323

DNA strand breaks pose the greatest threat to genomic stability. Genetically determined mutagen sensitivity predisposes individuals to a variety of cancers, including glioma. However, polymorphisms in DNA strand break repair genes that may determine mutagen sensitivity are not well studied in cancer risk, especially in gliomas.We correlated genotype data for tag single-nucleotide polymorphisms (tSNPs) of DNA strand break repair genes with a gamma-radiation-induced mutagen sensitivity phenotype [expressed as mean breaks per cell (B/C)] in samples from 426 glioma patients. We also conducted analysis to assess joint and haplotype effects of single-nucleotide polymorphisms (SNPs) on mutagen sensitivity. We further validate our results in an independent external control group totaling 662 subjects.Of the 392 tSNPs examined, we found that mutagen sensitivity was modified by one tSNP in the EME2 gene and six tSNPs in the RAD51L1 gene (P < 0.01). Among the six RAD51L1 SNPs tested in the validation set, one (RAD51L1 rs2180611) was significantly associated with mutagen sensitivity (P = 0.025). Moreover, we found a significant dose-response relationship between the mutagen sensitivity and the number of adverse tSNP genotypes. Furthermore, haplotype analysis revealed that RAD51L1 haplotypes F-A (zero adverse allele) and F-E (six adverse alleles) exhibited the lowest (0.42) and highest (0.93) mean B/C values, respectively. A similar dose-response relationship also existed between the mutagen sensitivity and the number of adverse haplotypes.These results suggest that polymorphisms in and haplotypes of the RAD51L1 gene, which is involved in the double-strand break repair pathway, modulate gamma-radiation-induced mutagen sensitivity.

Authors

Liu, Y; Shete, S; Wang, L-E; El-Zein, R; Etzel, CJ; Liang, F-W; Armstrong, G; Tsavachidis, S; Gilbert, MR; Aldape, KD; Xing, J; Wu, X; Wei, Q; Bondy, ML

MLA Citation

Liu, Y, Shete, S, Wang, L-E, El-Zein, R, Etzel, CJ, Liang, F-W, Armstrong, G, Tsavachidis, S, Gilbert, MR, Aldape, KD, Xing, J, Wu, X, Wei, Q, and Bondy, ML. "Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk." Carcinogenesis 31.10 (October 2010): 1762-1769.

PMID

20610542

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

10

Publish Date

2010

Start Page

1762

End Page

1769

DOI

10.1093/carcin/bgq141

Insulin-like growth factor binding protein 7 (IGFBP7) functions mostly independent of the IGF signaling pathway and acts as a tumor suppressor in multiple cancers, but roles of IGFBP7 genetic variants in cancer remains unknown. In a hospital-based study of 1065 patients with squamous cell carcinoma of head and neck (SCCHN) and 1112 cancer-free controls of non-Hispanic whites, we investigated associations between two putatively functional IGFBP7 promoter single nucleotide polymorphisms (SNPs) (-702G>C, rs11573014 and -418G>A, rs4075349) and SCCHN risk. A significantly lower SCCHN risk was observed in those subjects carrying -418AG (adjusted OR=0.82, 95% CI=0.67-0.99) and -418AG+AA (adjusted OR=0.82, 95% CI=0.69-0.99) genotypes than those carrying the -418GG genotype, but not for the -702G>C SNP. However, those subjects carrying two common homozygous genotypes of these two SNPs (-418GG and -702GG) had an increased risk (adjusted OR=1.21, 95% CI=1.00-1.46) than did those carrying variant genotypes (-418AG+AA and -702CG+CC). This increased risk was more evident in subgroups of never smokers and subjects with oral cancer. Further functional analysis showed that the IGFBP7 -418A allele had significantly higher promoter and DNA-protein binding activities than did the G allele, suggesting a tumor suppressor role of this allelic change in the SCCHN etiology. We conclude that the functional variant -418G>C in the IGFBP7 promoter is associated with reduced risk of SCCHN, likely by enhancing the IGFBP7 promoter and DNA-protein binding activities. Larger studies are needed to validate our findings.

Authors

Huang, Y-J; Niu, J; Liu, Z; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Huang, Y-J, Niu, J, Liu, Z, Wang, L-E, Sturgis, EM, and Wei, Q. "The functional IGFBP7 promoter -418G>A polymorphism and risk of head and neck cancer." Mutation research 702.1 (September 2010): 32-39.

PMID

20599521

Source

epmc

Published In

Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Volume

702

Issue

1

Publish Date

2010

Start Page

32

End Page

39

DOI

10.1016/j.mrgentox.2010.06.012

The increasing incidence of oral squamous cell carcinoma (OSCC) in young adults has been associated with sexually transmitted infections of human papillomavirus (HPV), particularly HPV16. Given the roles of p53 in tumor suppression and of HPV E6 and MDM2 oncoproteins in p53 degradation, we evaluated HPV16 L1 seropositivity and MDM2 promoter variants to examine their possible associations with OSCC risk in a case-control study of 325 patients and 335 cancer-free matched controls. Compared with individuals having MDM2-rs2279744 GT or GG genotypes and HPV16 L1 seronegativity, the TT genotype and HPV16 L1 seronegativity were found to be associated with an odds ratio (OR) of 1.25 [95% confidence interval (CI), 1.06-2.19] for OSCC risk, and GT/GG and HPV16 L1 seropositivity were associated with an OR of 2.81 (95% CI, 1.67-4.74). For those with both the TT genotype and HPV16 L1 seropositivity, the associated OR was 5.57 (95% CI, 2.93-10.6). Similar results were observed for the MDM2-rs937283 polymorphism. Moreover, there was a borderline significant or significant interaction between the individual or combined MDM2 genotypes of the two polymorphisms and HPV16 L1 seropositivity (P(int) = 0.060 for MDM2-rs2279744, P(int) = 0.009 for MDM2-rs937283, and P(int) = 0.005 for the combined MDM2 genotypes) on risk of OSCC. Notably, that effect modification was particularly pronounced in never smokers and never drinkers, and for oropharyngeal as opposed to oral cavity cancer. Taken together, our results indicate that the risk of OSCC associated with HPV16 L1 seropositivity is modified by MDM2 promoter polymorphisms.

Authors

Chen, X; Sturgis, EM; Lei, D; Dahlstrom, K; Wei, Q; Li, G

MLA Citation

Chen, X, Sturgis, EM, Lei, D, Dahlstrom, K, Wei, Q, and Li, G. "Human papillomavirus seropositivity synergizes with MDM2 variants to increase the risk of oral squamous cell carcinoma." Cancer research 70.18 (September 2010): 7199-7208.

PMID

20736372

Source

epmc

Published In

Cancer Research

Volume

70

Issue

18

Publish Date

2010

Start Page

7199

End Page

7208

DOI

10.1158/0008-5472.can-09-4733

Authors

Li, G; Huang, Z; Chen, X; Wei, Q

MLA Citation

Li, G, Huang, Z, Chen, X, and Wei, Q. "Role of human papillomavirus and cell cycle-related variants in squamous cell carcinoma of the oropharynx." Journal of Biomedical Research 24.5 (September 2010): 339-346.

Source

crossref

Published In

Journal of Biomedical Research

Volume

24

Issue

5

Publish Date

2010

Start Page

339

End Page

346

DOI

10.1016/S1674-8301(10)60047-4

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS).Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype.Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.

Authors

Guan, X; Yin, M; Wei, Q; Zhao, H; Liu, Z; Wang, L-E; Yuan, X; O'Reilly, MS; Komaki, R; Liao, Z

MLA Citation

Guan, X, Yin, M, Wei, Q, Zhao, H, Liu, Z, Wang, L-E, Yuan, X, O'Reilly, MS, Komaki, R, and Liao, Z. "Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy." BMC cancer 10 (August 16, 2010): 431-.

PMID

20712888

Source

epmc

Published In

BMC Cancer

Volume

10

Publish Date

2010

Start Page

431

DOI

10.1186/1471-2407-10-431

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (-1304T>G and -1044A>T) with the Taqman assay, and we found that compared with the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61-0.90 for TG, and OR = 0.62; 95% CI = 0.41-0.94 for GG] in an allele dose-response manner (adjusted P(trend) = 0.0005). Further stratification analysis showed that the protective role of the -1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the -1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted P(interaction) = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the -1304TT genotype. However, no significant association was observed between the -1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.

Authors

Liu, B; Chen, D; Yang, L; Li, Y; Ling, X; Liu, L; Ji, W; Wei, Y; Wang, J; Wei, Q; Wang, L; Lu, J

MLA Citation

Liu, B, Chen, D, Yang, L, Li, Y, Ling, X, Liu, L, Ji, W, Wei, Y, Wang, J, Wei, Q, Wang, L, and Lu, J. "A functional variant (-1304T>G) in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity." Carcinogenesis 31.8 (August 2010): 1405-1411.

PMID

20554746

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

8

Publish Date

2010

Start Page

1405

End Page

1411

DOI

10.1093/carcin/bgq126

Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases.We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption.Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < or =18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI > or =30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < or =18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers.In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Authors

Gaudet, MM; Olshan, AF; Chuang, S-C; Berthiller, J; Zhang, Z-F; Lissowska, J; Zaridze, D; Winn, DM; Wei, Q; Talamini, R; Szeszenia-Dabrowska, N; Sturgis, EM; Schwartz, SM; Rudnai, P; Eluf-Neto, J; Muscat, J; Morgenstern, H; Menezes, A; Matos, E; Bucur, A; Levi, F; Lazarus, P; La Vecchia, C; Koifman, S; Kelsey, K; Herrero, R; Hayes, RB; Franceschi, S; Wunsch-Filho, V; Fernandez, L; Fabianova, E; Daudt, AW; Dal Maso, L; Curado, MP; Chen, C; Castellsague, X; Benhamou, S; Boffetta, P; Brennan, P et al.

MLA Citation

Gaudet, MM, Olshan, AF, Chuang, S-C, Berthiller, J, Zhang, Z-F, Lissowska, J, Zaridze, D, Winn, DM, Wei, Q, Talamini, R, Szeszenia-Dabrowska, N, Sturgis, EM, Schwartz, SM, Rudnai, P, Eluf-Neto, J, Muscat, J, Morgenstern, H, Menezes, A, Matos, E, Bucur, A, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Kelsey, K, Herrero, R, Hayes, RB, Franceschi, S, Wunsch-Filho, V, Fernandez, L, Fabianova, E, Daudt, AW, Dal Maso, L, Curado, MP, Chen, C, Castellsague, X, Benhamou, S, Boffetta, P, and Brennan, P et al. "Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium." International journal of epidemiology 39.4 (August 2010): 1091-1102.

PMID

20123951

Source

epmc

Published In

International Journal of Epidemiology

Volume

39

Issue

4

Publish Date

2010

Start Page

1091

End Page

1102

DOI

10.1093/ije/dyp380

To investigate the association of expression and promoter methylation of tumor-suppressor genes with risk of ovarian cancer, we conducted a case-control study of 102 patients with serous epithelial ovarian cancer and 100 patients without ovarian cancers. We measured mRNA expression levels (by real-time reverse transcription polymerase chain reaction) and methylation status (by methylation-specific polymerase chain reaction) of five candidate genes (BRCA1, BRCA2, hMLH1, MGMT, and DNMT3B) in tumors from the cases and normal ovaries from the controls. We found that mRNA expression levels of the five genes were decreased in tumors than in normal ovaries with 0.39-fold for BRCA1, 0.25-fold for BRCA2, 0.42-fold for hMLH1, 0.45-fold for MGMT, and 0.87-fold for DNMT3B, calculated by the 2-δδCT method. Ovarian cancer risk (odds ratios, ORs) was associated with low expression of all genes (2.95 [95% confidence interval (CI), 1.51 - 5.78] for BRCA1, 3.65 (95% CI, 1.82 - 7.30) for BRCA2, 5.25 (95% CI, 2.52 - 10.96) for hMLH1, and 4.72 (95% CI, 2.32 - 9.62) for MGMT) but not DNMT3B. However, methylation status was not associated with gene expression levels in the tumors, except for hMLH1 whose mean (± SD) gene expression was significantly lower in methylated (13.0 ± 7.6) than in unmethylated (31.2 ± 44.8) tumors (P < 0.001). We concluded that low mRNA expression of these tumorsuppressor genes, likely due to molecular mechanisms in addition to the promoter methylation in some instances, may be a biomarker for ovarian cancer risk in this study population. Larger studies are needed to validate our findings.

Authors

An, J; Wei, Q; Liu, Z; Lu, KH; Cheng, X; Mills, GB; Wang, LE

MLA Citation

An, J, Wei, Q, Liu, Z, Lu, KH, Cheng, X, Mills, GB, and Wang, LE. "Messenger rna expression and methylation of candidate tumor-suppressor genes and risk of ovarian cancer-a case-control analysis." International Journal of Molecular Epidemiology and Genetics 1.1 (July 21, 2010): 1-10.

Source

scopus

Published In

International Journal of Molecular Epidemiology and Genetics

Volume

1

Issue

1

Publish Date

2010

Start Page

1

End Page

10

Authors

Kehoe, PG; Ambrosone, CB; Arnett, DK; Cerhan, JR; Pedersen, N; Wei, Q; Wang, D

MLA Citation

Kehoe, PG, Ambrosone, CB, Arnett, DK, Cerhan, JR, Pedersen, N, Wei, Q, and Wang, D. "The launch of international journal of molecular epidemiology and genetics." International Journal of Molecular Epidemiology and Genetics 1.1 (July 21, 2010).

Source

scopus

Published In

International Journal of Molecular Epidemiology and Genetics

Volume

1

Issue

1

Publish Date

2010

Elevated levels of human telomerase (hTERT) mRNA in tumors is a marker for poorer survival in patients with stage I non-small cell lung cancer (NSCLC). A functional variant of MNS16A-short tandem repeats in hTERT (S allele) is associated with higher expression levels of hTERT mRNA compared with the MNS16A-long (L) allele. It is unknown, however, whether or not the hTERT MNS16A variant genotype predicts survival of NSCLC patients.The hTERT genotypes of 808 patients with NSCLC were determined by direct PCR with genomic DNA. Overall median survival times were estimated by the life-table method, and the log-rank test was used to test for homogeneity of the survival curves. Both univariate and multivariate Cox proportional hazards models were used to assess the associations between survival time and the hTERT genotype as well as other known risk factors.The hTERT variant genotype was not associated with overall survival among the 808 patients. However, among 221 patients with stage I or II NSCLC, the S allele was associated with shorter survival time (P = 0.027, by log-rank test). The adjusted hazard ratios were 1.30 (95% confidence interval, 0.79-2.14; P = 0.310) for the SL-genotype and 2.34 (95% confidence interval, 1.20-4.56, P = 0.012) for the SS-genotype compared with the LL-genotype (P = 0.021 for trend test). These findings were not evident in 587 patients with stage III or IV NSCLC.The functional MNS16A-SS genotype may be a marker for poorer survival in early-stage NSCLC.

Authors

Wang, L; Wang, L-E; Mao, L; Spitz, MR; Wei, Q

MLA Citation

Wang, L, Wang, L-E, Mao, L, Spitz, MR, and Wei, Q. "A functional variant of tandem repeats in human telomerase gene was associated with survival of patients with early stages of non-small cell lung cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 16.14 (July 2010): 3779-3785.

PMID

20466886

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

16

Issue

14

Publish Date

2010

Start Page

3779

End Page

3785

DOI

10.1158/1078-0432.ccr-10-0269

Checkpoint kinase (CHEK) 2, a tumor suppressor gene, plays an essential role in the DNA damage checkpoint response cascade. We first investigated two polymorphisms in the proximal promoter of the CHEK2 gene and evaluated their associations with the risk of lung cancer in a case-control study using 500 incident lung cancer cases and 517 cancer-free controls. We found that CHEK2 rs2236141 -48 G > A was significantly associated with lung cancer risk (P = 0.0018). Similar results were obtained in a follow-up replication study in 575 lung cancer patients and 589 controls (P = 0.042). Quantitative polymerase chain reaction showed that individuals with the G allele had lower levels of CHEK2 transcripts in peripheral blood mononuclear cells and normal lung tissues. The -48 G-->A variant eliminated a methylation site and thereby relieve the transcriptional repression of CHEK2. Therefore, this polymorphism affected downstream transcription through genetic and epigenetic modifications. Luciferase reporter assays demonstrated that the major G allele significantly attenuated reporter gene expression when methylated. Electrophoretic Mobility shift assays and surface plasmon resonance revealed that the methylated G allele increased transcription factor accessibility. We used in vivo chromatin immunoprecipitation to confirm that the relevant transcription factor was Sp1. Using lung tissue heterozygous for the G/A single-nucleotide polymorphism, we found that Sp1 acted as a repressor and had a stronger binding affinity for the G allele. These results support our hypothesis that the CHEK2 rs2236141 variant modifies lung cancer susceptibility in the Chinese population by affecting CHEK2 expression.

Authors

Zhang, S; Lu, J; Zhao, X; Wu, W; Wang, H; Lu, J; Wu, Q; Chen, X; Fan, W; Chen, H; Wang, F; Hu, Z; Jin, L; Wei, Q; Shen, H; Huang, W; Lu, D

MLA Citation

Zhang, S, Lu, J, Zhao, X, Wu, W, Wang, H, Lu, J, Wu, Q, Chen, X, Fan, W, Chen, H, Wang, F, Hu, Z, Jin, L, Wei, Q, Shen, H, Huang, W, and Lu, D. "A variant in the CHEK2 promoter at a methylation site relieves transcriptional repression and confers reduced risk of lung cancer." Carcinogenesis 31.7 (July 2010): 1251-1258.

PMID

20462940

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

7

Publish Date

2010

Start Page

1251

End Page

1258

DOI

10.1093/carcin/bgq089

PIN1, an isomerase that causes conformational changes in proteins, plays an important role in mammary epithelial cell growth both physiologically and pathologically. Thus, genetic variants in the PIN1 gene may alter protein function and cancer risk. We have previously demonstrated an association between a PIN1 promoter variant (-842G>C; rs2233678) and risk of squamous cell carcinoma of the head and neck, a finding supported by additional functional data. In the present study, we genotyped two promoter single nucleotide polymorphisms (SNPs) (-842G>C, rs2233678 and -667T>C, rs2233679) and one synonymous SNP (Gln33Gln; G>A, rs2233682) in exon 2 to evaluate their associations with risk of sporadic breast cancer in non-Hispanic white women 55 years and younger. We found that the carriers of -842C variant alleles had decreased risk of breast cancer with an adjusted odd ratio (OR) of 0.67 and 95% confidence interval (CI) of 0.50-0.90. This reduced risk was more evident in women after reproductive age of 45 (OR = 0.63, 95% CI = 0.42-0.93), ever-smokers (OR = 0.56, 95% CI = 0.36-0.88), and ever-drinkers (OR = 0.67, 95% CI = 0.45-0.99). No such associations were observed for PIN1 -667T>C and PIN1 Gln33Gln. However, the haplotypes of these three SNPs were also associated with reduced risk of breast cancer. In conclusion, the PIN1 polymorphisms may contribute to the etiology of sporadic breast cancer in non-Hispanic white women 55 years and younger. Further validation in large population-based studies is needed.

Authors

Han, CH; Lu, J; Wei, Q; Bondy, ML; Brewster, AM; Yu, T-K; Buchholz, TA; Arun, BK; Wang, L-E

MLA Citation

Han, CH, Lu, J, Wei, Q, Bondy, ML, Brewster, AM, Yu, T-K, Buchholz, TA, Arun, BK, and Wang, L-E. "The functional promoter polymorphism (-842G>C) in the PIN1 gene is associated with decreased risk of breast cancer in non-Hispanic white women 55 years and younger." Breast cancer research and treatment 122.1 (July 2010): 243-249.

PMID

20033770

Source

epmc

Published In

Breast Cancer Research and Treatment

Volume

122

Issue

1

Publish Date

2010

Start Page

243

End Page

249

DOI

10.1007/s10549-009-0682-9

The authors conducted a hospital-based study of 1110 patients with squamous cell carcinoma of the head and neck (SCCHN) and a control group of 1129 patients to replicate the associations reported by a recent, large European study between 2 potentially functional single nucleotide polymorphisms (SNPs) of the alcohol dehydrogenase (ADH) genes, a substitution in ADH1B at amino acid 48 from arginine to histidine (R48H) (reference SNP number [rs]1229984; guanine to adenine [G-->A]) and a substitution in ADH7 at amino acid 92 from alanine to glycine (A92G) (rs1573496; cytosine to guanine [C-->G]), and the risk of squamous cell carcinoma of the head and neck (SCCHN).Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). False-positive report probabilities (FPRPs) also were calculated for significant findings.The ADH7 A92G GG and combined CG + GG genotypes were associated with a decreased risk of SCCHN (GG: adjusted OR, 0.32; 95% CI, 0.13-0.82; CG + GG: adjusted OR, 0.74; 95% CI, 0.59-0.94; FPRP, .098) compared with the CC genotype. This association was also evident in subgroups of older patients (aged >57 years), men, former smokers, patients with oral cancer, and patients with N) lymph node status (P < .05 for all); however, such associations were not observed for the ADH1B R48H SNP.The current results support the ADH7 A92G SNP as a marker for the risk of SCCHN in non-Hispanic white populations.

Authors

Wei, S; Liu, Z; Zhao, H; Niu, J; Wang, L-E; El-Naggar, AK; Sturgis, EM; Wei, Q

MLA Citation

Wei, S, Liu, Z, Zhao, H, Niu, J, Wang, L-E, El-Naggar, AK, Sturgis, EM, and Wei, Q. "A single nucleotide polymorphism in the alcohol dehydrogenase 7 gene (alanine to glycine substitution at amino acid 92) is associated with the risk of squamous cell carcinoma of the head and neck." Cancer 116.12 (June 2010): 2984-2992.

PMID

20336794

Source

epmc

Published In

Cancer

Volume

116

Issue

12

Publish Date

2010

Start Page

2984

End Page

2992

DOI

10.1002/cncr.25058

Single-nucleotide polymorphisms in the promoter region of the FAS and FASLG may alter the transcriptional activity of these genes. We therefore investigated the association between the FAS and FASLG polymorphisms and risk for second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN).We used log-rank test and Cox proportional hazard models to assess the association of the four single-nucleotide polymorphisms (FAS -1377 G > A, FAS -670 A > G, FASLG -844 C > T, and FASLG -124 A > G) with the SPM-free survival and SPM risk among 1,286 incident SCCHN patients.Compared with patients having the FAS -670 AA or the FASLG -844 CC genotypes, the patients having variant genotypes of FAS -670 AG/GG or FASLG -844 CT/TT genotypes had significantly increased risk for SPM, respectively. A trend for significantly increased SPM risk with increasing number of risk genotypes of the four polymorphisms was observed in a dose-response manner. Moreover, the patients with three or four combined risk genotypes had an approximately 1.8- or 2.5-fold increased risk for developing SPM compared with patients with zero or one risk genotypes, respectively.Our results suggest a modestly increased risk for SPM after index SCCHN with FAS -670 A > G and FASLG -844 C > T polymorphisms and an even greater risk for SPM with multiple combined FAS and FASLG risk genotypes.The FAS and FASLG polymorphisms may serve as a susceptible marker for SCCHN patients at high SPM risk.

Authors

Lei, D; Sturgis, EM; Wang, L-E; Liu, Z; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Lei, D, Sturgis, EM, Wang, L-E, Liu, Z, Zafereo, ME, Wei, Q, and Li, G. "FAS and FASLG genetic variants and risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19.6 (June 2010): 1484-1491.

PMID

20501759

Source

epmc

Published In

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Volume

19

Issue

6

Publish Date

2010

Start Page

1484

End Page

1491

DOI

10.1158/1055-9965.epi-10-0030

Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.

Authors

Lubin, JH; Gaudet, MM; Olshan, AF; Kelsey, K; Boffetta, P; Brennan, P; Castellsague, X; Chen, C; Curado, MP; Dal Maso, L; Daudt, AW; Fabianova, E; Fernandez, L; Wünsch-Filho, V; Franceschi, S; Herrero, R; Koifman, S; La Vecchia, C; Lazarus, P; Levi, F; Lissowska, J; Mates, IN; Matos, E; McClean, M; Menezes, A; Morgenstern, H; Muscat, J; Eluf Neto, J; Purdue, MP; Rudnai, P; Schwartz, SM; Shangina, O; Sturgis, EM; Szeszenia-Dabrowska, N; Talamini, R; Wei, Q; Winn, D; Zhang, Z-F; Hashibe, M et al.

MLA Citation

Lubin, JH, Gaudet, MM, Olshan, AF, Kelsey, K, Boffetta, P, Brennan, P, Castellsague, X, Chen, C, Curado, MP, Dal Maso, L, Daudt, AW, Fabianova, E, Fernandez, L, Wünsch-Filho, V, Franceschi, S, Herrero, R, Koifman, S, La Vecchia, C, Lazarus, P, Levi, F, Lissowska, J, Mates, IN, Matos, E, McClean, M, Menezes, A, Morgenstern, H, Muscat, J, Eluf Neto, J, Purdue, MP, Rudnai, P, Schwartz, SM, Shangina, O, Sturgis, EM, Szeszenia-Dabrowska, N, Talamini, R, Wei, Q, Winn, D, Zhang, Z-F, and Hashibe, M et al. "Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data." American journal of epidemiology 171.12 (June 2010): 1250-1261.

PMID

20494999

Source

epmc

Published In

American Journal of Epidemiology

Volume

171

Issue

12

Publish Date

2010

Start Page

1250

End Page

1261

DOI

10.1093/aje/kwq088

Methylating agents are involved in carcinogenesis, and the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O(6)-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case-control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C>T and 16286C>T and two in the promoter region, 45996G>T and 46346C>A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT+TT, and 46346CA+AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR)=1.27; 95% confidence interval (CI)=1.05-1.53). This increased risk was also more pronounced among young subjects (OR=1.81; 95% CI=1.11-2.96), men (OR=1.24; 95% CI=1.00-1.55), ever smokers (OR=1.25; 95%=1.01-1.56), ever drinkers (OR=1.29; 95% CI=1.04-1.60), patients with oropharyngeal cancer (OR=1.45; 95% CI=1.12-1.87), and oropharyngeal cancer with regional lymph node metastasis (OR=1.52; 95% CI=1.16-1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites.

Authors

Zhang, Z; Wang, L; Wei, S; Liu, Z; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Zhang, Z, Wang, L, Wei, S, Liu, Z, Wang, L-E, Sturgis, EM, and Wei, Q. "Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer." DNA repair 9.5 (May 2010): 558-566.

PMID

20206583

Source

epmc

Published In

DNA Repair

Volume

9

Issue

5

Publish Date

2010

Start Page

558

End Page

566

DOI

10.1016/j.dnarep.2010.02.006

p53 plays a critical role in cellular anticancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 of p53 results in an amino acid substitution and could influence p53 function. The authors hypothesized that p53 codon 72 polymorphism may be associated with risk of SPMs and SPM-free survival among patients with squamous cell carcinoma of the head and neck (SCCHN).A total of 1271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and observed for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups.The authors found significantly reduced SPM-free survival for patients with variant proline (Pro) 72 allele compared with patients with arginine (Arg) 72 homozygous genotype (log-rank test, P = .005). Compared with SCCHN patients with the p53 72Arg/Arg genotype, there was a significantly greater risk of SPM associated with the p53 72Arg/Pro genotype (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.17-2.61) and combined p53 72Arg/Pro + Pro/Pro (HR, 1.58; 95% CI, 1.07-2.34). Furthermore, stratification analyses showed that the risk of SPM associated with p53 variant genotypes (Arg/Pro + Pro/Pro) was more pronounced in several subgroups.p53 codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM in patients with primary SCCHN.

Authors

Li, F; Sturgis, EM; Chen, X; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Li, F, Sturgis, EM, Chen, X, Zafereo, ME, Wei, Q, and Li, G. "Association of p53 codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck." Cancer 116.10 (May 2010): 2350-2359.

PMID

20225330

Source

epmc

Published In

Cancer

Volume

116

Issue

10

Publish Date

2010

Start Page

2350

End Page

2359

DOI

10.1002/cncr.25072

Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results. We performed a meta-analysis of 23 publications with a total of 55 174 cancer cases and 59 336 controls from 55 individual studies. We summarized the data on the associations between three studied CASP8 polymorphisms (G>C D302H, -652 6N del and Ex14-271A>T) and cancer risk and performed subgroup analysis by ethnicity, cancer type, study design and etiology. We found that D302H CC and CG variant genotypes were associated with significantly reduced overall risk of cancers using conservative random genetic models [homozygote comparison: odds ratios (OR) = 0.79; 95% confidence interval (CI): 0.69-0.92; dominant comparison: OR = 0.93, 95% CI: 0.89-0.98; recessive comparison: OR = 0.81, 95% CI: 0.71-0.93). In further stratified analyses, the reduced cancer risk remained for subgroups of Caucasians, breast or estrogen-related cancers, and hospital- or population-based studies, except for an elevated risk for brain tumors. Similarly, the -652 6N del polymorphism was also associated with significantly reduced overall risk of cancers (homozygote comparison: OR = 0.84, 95% CI: 0.75-0.94; dominant comparison: OR = 0.88, 95% CI: 0.81-0.96; recessive comparison: OR = 0.90, 95% CI: 0.82-0.99) and all subgroups analyzed. However, the Ex14-271A>T polymorphism did not appear to have an effect on cancer risk. These results suggest that CASP8 D302H and -652 6N del polymorphisms are potential biomarkers for cancer risk.

Authors

Yin, M; Yan, J; Wei, S; Wei, Q

MLA Citation

Yin, M, Yan, J, Wei, S, and Wei, Q. "CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studies." Carcinogenesis 31.5 (May 2010): 850-857.

PMID

20176653

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

5

Publish Date

2010

Start Page

850

End Page

857

DOI

10.1093/carcin/bgq047

Xeroderma pigmentosum group F (XPF) has an essential role in the nucleotide excision repair pathway that removes a wide variety of DNA lesions. We hypothesized that genetic variants in XPF are associated with bladder cancer risk and recurrence. We selected three tagging single nucleotide polymorphisms (tagSNPs) from the HapMap database for the Chinese and genotyped them in a two-stage case-control study to evaluate the association and further examined the functionality of a novel polymorphism in the promoter. The two-stage analysis found that the rs744154 tagSNP in the XPF intron 1, which was linkage disequilibrium with the -357A>C polymorphism in the promoter region, was associated with a protective effect on bladder cancer risk. Electrophoretic mobility shift assay (EMSA) further revealed that the -357C allele decreased the binding ability of transcriptional factors to the XPF promoter. The vector construct containing the -357C allele had a lower luciferase expression than did the -357A allele. The -357C allele in the transcription factor-binding site was also associated with decreased expression levels of both XPF mRNA and protein in bladder cancer tissues. Furthermore, patients with the -357C allele had a shorter overall recurrence-free survival than did patients with the -357A allele. Our results suggest that the XPF promoter -357A>C polymorphism may regulate the expression of XPF and thereby contribute to susceptibility to and prognosis of bladder cancer. Further larger studies with different populations are warranted to confirm these findings.

Authors

Wang, M; Wang, M; Yuan, L; Wu, D; Zhang, Z; Yin, C; Fu, G; Wei, Q; Zhang, Z

MLA Citation

Wang, M, Wang, M, Yuan, L, Wu, D, Zhang, Z, Yin, C, Fu, G, Wei, Q, and Zhang, Z. "A novel XPF -357A>C polymorphism predicts risk and recurrence of bladder cancer." Oncogene 29.13 (April 2010): 1920-1928.

PMID

20062074

Source

epmc

Published In

Oncogene: Including Oncogene Reviews

Volume

29

Issue

13

Publish Date

2010

Start Page

1920

End Page

1928

DOI

10.1038/onc.2009.484

Transforming growth factor-beta1 (TGF-beta1) plays an important role in inflammation and immune responses, which control the human papillomavirus (HPV) clearance and escape of immune surveillance, and may contribute to genetic susceptibility to HPV16 infection.In this case series study, we analyzed the HPV16 status in tumor specimens and genotyped three TGF-beta1 polymorphisms using genomic DNA from the blood of 200 squamous cell carcinoma of the oropharynx (SCCOP) cases. We calculated odds ratio (OR) and 95% confidence intervals (95% CI) in univariate and multivariable logistic regression models to examine the association between the TGF-beta1 polymorphisms and HPV16 status in SCCOP.Compared with those with the common homozygous genotype, the TGF-beta1 T869C variant genotypes were significantly associated with HPV16-positive tumor status among patients with SCCOP (OR, 1.97; 95% CI, 1.03-3.76), but no significant association was observed for the TGF-beta1 C509T or G915C polymorphism. When all variant genotypes were combined, however, SCCOP patients carrying genotypes with any of these TGF-beta1 variants were more than twice as likely to have an HPV16-positive tumor (OR, 2.28; 95% CI, 1.16-4.50) as patients with no variant genotypes. The stratified analysis showed that those under 54 years of age, non-Hispanic white patients, never smokers, and never drinkers with any variant TGF-beta1 genotypes were also more likely to have HPV16-positive tumors.TGF-beta1 polymorphisms may serve as a susceptibility marker for tumor HPV16 status among SCCOP patients, particularly those who were never smokers and never drinkers. Large studies are needed to validate our findings.

Authors

Guan, X; Sturgis, EM; Lei, D; Liu, Z; Dahlstrom, KR; Wei, Q; Li, G

MLA Citation

Guan, X, Sturgis, EM, Lei, D, Liu, Z, Dahlstrom, KR, Wei, Q, and Li, G. "Association of TGF-beta1 genetic variants with HPV16-positive oropharyngeal cancer." Clinical cancer research : an official journal of the American Association for Cancer Research 16.5 (March 2010): 1416-1422.

PMID

20179236

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

16

Issue

5

Publish Date

2010

Start Page

1416

End Page

1422

DOI

10.1158/1078-0432.ccr-09-2877

p21 plays an important role in modulating cell cycle control, inducing apoptosis, and inhibiting cell growth, subsequently affecting cancer risk. We investigated the association between two putatively functional single-nucleotide polymorphisms (SNPs) of p21 (p21 C98A and p21 C70T) among 1282 patients diagnosed with incident squamous cell carcinoma of the head and neck (SCCHN) and risk of second primary malignancy (SPM) in an ongoing molecular epidemiology study. We used Log-rank test and Cox proportional hazard models to assess the association of these two SNPs with SPM-free survival and SPM risk. We found that patients with either p21 variant genotypes of the two polymorphisms had a significantly reduced SPM-free survival compared with patients with either p21 wild-type homozygous genotypes (Log-rank test, P = 0.0016). Compared with patients having the p21 98 CC and p21 70 CC genotypes, the patients having p21 98 CA/AA and p21 70 CT/TT variant genotypes had a significantly greater risk of developing SPM, respectively, [hazard ratio (HR) = 1.80, 95% CI = 1.14-2.82 for p21 C98A and HR = 1.82, 95% confidence interval (CI) = 1.16-2.85 for p21 C70T]. Moreover, after combining the variant genotypes of two SNPs, patients with variant genotypes had a significantly moderately increased risk for SPM compared with patients with no variant genotypes (HR = 2.00, 95% CI = 1.26-3.00), and the risk was particularly pronounced in several subgroups. Our results support an increased risk of SPM after index SCCHN with both p21 polymorphisms individually and in combination.

Authors

Lei, D; Sturgis, EM; Liu, Z; Zafereo, ME; Wei, Q; Li, G

MLA Citation

Lei, D, Sturgis, EM, Liu, Z, Zafereo, ME, Wei, Q, and Li, G. "Genetic polymorphisms of p21 and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck." Carcinogenesis 31.2 (February 2010): 222-227.

PMID

19955391

Source

epmc

Published In

Carcinogenesis

Volume

31

Issue

2

Publish Date

2010

Start Page

222

End Page

227

DOI

10.1093/carcin/bgp279

Caspase 8 (CASP8) is an apoptosis-related cysteine peptidase involved in the death receptor pathway and likely in the mitochondrial pathway. A CASP8 promoter region six-nucleotide deletion/insertion (-652 6N ins/del) variant and a coding region D302H polymorphism are reportedly important in cancer development, but no reported study has assessed the associations of these genetic variations with risk of head and neck cancer. In a hospital-based study of non-Hispanic whites, we genotyped CASP8 -652 6N del and 302H variants in 1,023 patients with squamous cell carcinoma of the head and neck (SCCHN) and 1,052 cancer-free controls. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models. The CASP8 -652 6N del variant genotypes or haplotypes were inversely associated with SCCHN risk (adjusted OR, 0.70; 95% CI, 0.57-0.85 for the ins/del + del/del genotypes compared with the ins/ins genotype; adjusted OR, 0.73; 95% CI, 0.55-0.97 for the del-D haplotype compared with the ins-D haplotype). Furthermore, the number of the CASP8 -652 6N del (but not 302H) variant allele tended to correlate with increased levels of camptothecin-induced p53-mediated apoptosis in T lymphocytes from 170 cancer-free controls. We concluded that the CASP8 -652 6N del variant allele may contribute to the risk of developing SCCHN in non-Hispanic white populations. Further validation by population-based case-control studies and rigorous mechanistic studies is warranted.

Authors

Li, C; Lu, J; Liu, Z; Wang, L-E; Zhao, H; El-Naggar, AK; Sturgis, EM; Wei, Q

MLA Citation

Li, C, Lu, J, Liu, Z, Wang, L-E, Zhao, H, El-Naggar, AK, Sturgis, EM, and Wei, Q. "The six-nucleotide deletion/insertion variant in the CASP8 promoter region is inversely associated with risk of squamous cell carcinoma of the head and neck." Cancer prevention research (Philadelphia, Pa.) 3.2 (February 2010): 246-253.

PMID

20086182

Source

epmc

Published In

Cancer Prevention Research

Volume

3

Issue

2

Publish Date

2010

Start Page

246

End Page

253

DOI

10.1158/1940-6207.capr-08-0228

Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers.We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models.Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers.Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.

Authors

Marron, M; Boffetta, P; Zhang, Z-F; Zaridze, D; Wünsch-Filho, V; Winn, DM; Wei, Q; Talamini, R; Szeszenia-Dabrowska, N; Sturgis, EM; Smith, E; Schwartz, SM; Rudnai, P; Purdue, MP; Olshan, AF; Eluf-Neto, J; Muscat, J; Morgenstern, H; Menezes, A; McClean, M; Matos, E; Mates, IN; Lissowska, J; Levi, F; Lazarus, P; La Vecchia, C; Koifman, S; Kelsey, K; Herrero, R; Hayes, RB; Franceschi, S; Fernandez, L; Fabianova, E; Daudt, AW; Dal Maso, L; Curado, MP; Cadoni, G; Chen, C; Castellsague, X; Boccia, S et al.

MLA Citation

Marron, M, Boffetta, P, Zhang, Z-F, Zaridze, D, Wünsch-Filho, V, Winn, DM, Wei, Q, Talamini, R, Szeszenia-Dabrowska, N, Sturgis, EM, Smith, E, Schwartz, SM, Rudnai, P, Purdue, MP, Olshan, AF, Eluf-Neto, J, Muscat, J, Morgenstern, H, Menezes, A, McClean, M, Matos, E, Mates, IN, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Kelsey, K, Herrero, R, Hayes, RB, Franceschi, S, Fernandez, L, Fabianova, E, Daudt, AW, Dal Maso, L, Curado, MP, Cadoni, G, Chen, C, Castellsague, X, and Boccia, S et al. "Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk." International journal of epidemiology 39.1 (February 2010): 182-196.

PMID

19805488

Source

epmc

Published In

International Journal of Epidemiology

Volume

39

Issue

1

Publish Date

2010

Start Page

182

End Page

196

DOI

10.1093/ije/dyp291

The migration and invasion inhibitory protein MIIP is an inhibitor of cancer cell migration and invasion that inhibits breast tumorigenesis. In this case-control study, we evaluated the MIIP single nucleotide polymorphism (SNP) rs2295283 (codon 167, A>G, K>E) from 1,524 breast cancer patients and 1,592 age-matched controls for its association with breast cancer risk. SNP analysis included a validation set of 736 cases and 760 controls. Colony formation and cell migration assays were then conducted to functionally interrogate the genotype difference. When compared with the AA genotype, the combined AG + GG genotypes (167E) were associated with a significantly lower risk of breast cancer. In the test set, the protective effects of the AG + GG genotypes were more evident among participants with a family history of cancer. Further case series analysis revealed that the GG genotype was associated with reduced breast cancer susceptibility in cases of tumor size >2 cm and late clinical stage (II + III + IV). Colony formation assays showed that MIIP 167E (the G variant) was a more potent inhibitor of colony formation but not cell migration. These results suggest MIIP K167E as a functional genetic marker of breast cancer development and prognosis.

Authors

Song, F; Ji, P; Zheng, H; Song, F; Wang, Y; Hao, X; Wei, Q; Zhang, W; Chen, K

MLA Citation

Song, F, Ji, P, Zheng, H, Song, F, Wang, Y, Hao, X, Wei, Q, Zhang, W, and Chen, K. "Definition of a functional single nucleotide polymorphism in the cell migration inhibitory gene MIIP that affects the risk of breast cancer." Cancer research 70.3 (February 2010): 1024-1032.

PMID

20103646

Source

epmc

Published In

Cancer Research

Volume

70

Issue

3

Publish Date

2010

Start Page

1024

End Page

1032

DOI

10.1158/0008-5472.can-09-3742

Although cigarette smoking and alcohol use are known risk factors for squamous cell carcinoma of head and neck (SCCHN), only a few exposed individuals develop this disease, suggesting an individual susceptibility. In this study, we investigated the associations between genetically determined DNA repair capacity (DRC) for removing tobacco-induced DNA adducts and risk of SCCHN and tumor characteristics.We measured DRC in cultured T lymphocytes using the host-cell reactivation assay in a hospital-based case-control study of 744 SCCHN patients and 753 age-, sex-, and ethnicity-matched cancer-free controls recruited from The University of Texas M.D. Anderson Cancer Center.Patients with SCCHN had significantly lower mean DRC (8.84% +/- 2.68%) than controls (9.97% +/- 2.61%; P < 0.0001), and the difference accounted for approximately 2-fold increased risk of SCCHN [adjusted odds ratio (OR), 1.91; 95% confidence interval (CI), 1.52-2.40] after adjustment for other covariates. Compared with the highest DRC quartile of controls, this increased risk was dose dependent (second highest quartile: OR, 1.40; 95% CI, 0.99-1.98; third quartile: OR, 1.87; 95% CI, 1.34-2.62; and fourth quartile: OR, 2.76; 95% CI, 1.98-3.84, respectively; P(trend) < 0.0001). We also assessed the performance of DRC in risk prediction models by calculating the area of under the receiver operating characteristic curve. The addition of DRC to the model significantly improved the sensitivity of the expanded model. However, we did not find the association between DRC and tumor sites and stages.DRC is an independent susceptibility biomarker for SCCHN risk but not a tumor marker.

Authors

Wang, L-E; Hu, Z; Sturgis, EM; Spitz, MR; Strom, SS; Amos, CI; Guo, Z; Qiao, Y; Gillenwater, AM; Myers, JN; Clayman, GL; Weber, RS; El-Naggar, AK; Mao, L; Lippman, SM; Hong, WK; Wei, Q

MLA Citation

Wang, L-E, Hu, Z, Sturgis, EM, Spitz, MR, Strom, SS, Amos, CI, Guo, Z, Qiao, Y, Gillenwater, AM, Myers, JN, Clayman, GL, Weber, RS, El-Naggar, AK, Mao, L, Lippman, SM, Hong, WK, and Wei, Q. "Reduced DNA repair capacity for removing tobacco carcinogen-induced DNA adducts contributes to risk of head and neck cancer but not tumor characteristics." Clinical cancer research : an official journal of the American Association for Cancer Research 16.2 (January 12, 2010): 764-774.

PMID

20068090

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

16

Issue

2

Publish Date

2010

Start Page

764

End Page

774

DOI

10.1158/1078-0432.ccr-09-2156

p21 (WAF1/Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can induce cell cycle arrest and serve as tumor suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to pancreatic cancer.To test this hypothesis, we evaluated the associations of the Ser31Arg polymorphism in p21 and the Gly109Val polymorphism in p27, and their combinations, with pancreatic cancer risk in a case-control study of 509 pathologically confirmed pancreatic adenocarcinoma patients and 462 age- and sex-matched cancer-free controls in non-Hispanic whites.We found that the heterozygous and homozygous variant genotypes combined in a dominant model of the p21 polymorphism were associated with increased risk of pancreatic cancer compared with the homozygous wild type (adjusted odds ratio [ORadjusted], 1.70; 95% confidence interval [CI], 1.13-2.55). This increased risk was more pronounced in carriers with the p27 homozygous wild type (ORadjusted, 2.20; 95% CI, 1.32-3.68) and in nonsmokers (ORadjusted, 2.16; 95% CI, 1.14-4.10), although the p27 polymorphism alone was not associated with pancreatic cancer risk.These results indicate that the p21 polymorphism may contribute to susceptibility to pancreatic cancer, particularly among p27 homozygous wild-type carriers and nonsmokers.

Authors

Chen, J; Amos, CI; Merriman, KW; Wei, Q; Sen, S; Killary, AM; Frazier, ML

MLA Citation

Chen, J, Amos, CI, Merriman, KW, Wei, Q, Sen, S, Killary, AM, and Frazier, ML. "Genetic variants of p21 and p27 and pancreatic cancer risk in non-Hispanic Whites: a case-control study." Pancreas 39.1 (January 2010): 1-4.

PMID

19910837

Source

epmc

Published In

Pancreas

Volume

39

Issue

1

Publish Date

2010

Start Page

1

End Page

4

DOI

10.1097/mpa.0b013e3181bd51c8

Survivin has been identified as an apoptosis inhibitor and a key regulator of mitosis. A common polymorphism (-31G > C) at the survivin promoter has been extensively studied in various cancers and reported to influence survivin expression. We hypothesize that polymorphisms in the survivin promoter are associated with clinical outcomes of patients with ovarian cancer. In this study, we genotyped all of five common and independent (r 2 < 0.25 for all LD) survivin promoter polymorphisms (-1547A/G [rs3764383], -644C/T [rs8073903] , -625C/G [rs8073069], -241C/T [rs17878467] , and -31G/C [rs9904341]) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method. We found that -1547A/G and -31G/C were significantly associated with age of disease onset. Compared with patients with the -1547GG genotype, the -1547AA genotype showed a significantly younger age of disease onset (58.8 years vs. 70.1 years; P = 0.001); the -31CC genotype had a decrease, though not significant, in the age of disease onset, compared with patients with the -31GG genotype (57.1 years vs. 62.8 years; P = 0.058). The numbers of -1547A and -31C alleles were associated with a decrease in age of onset in an allele-dose response manner (P trend = 0.001 and 0.026, respectively). However, no association was found between survivin polymorphisms and patients' prognosis, except for -625C/G SNP in 37 patients with a persistent disease. The findings suggest that the promoter variants of survivin may have an effect on age of onset of ovarian cancer. Validation studies with larger sample sizes are warranted.

Authors

Han, CH; Wei, Q; Lu, KK; Liu, Z; Mills, GB; Wang, LE

MLA Citation

Han, CH, Wei, Q, Lu, KK, Liu, Z, Mills, GB, and Wang, LE. "Polymorphisms in the survivin promoter are associated with age of onset of ovarian cancer." International Journal of Clinical and Experimental Medicine 2.4 (December 1, 2009): 289-299.

Source

scopus

Published In

International Journal of Clinical and Experimental Medicine

Volume

2

Issue

4

Publish Date

2009

Start Page

289

End Page

299

P73 plays an important role in modulating cell-cycle control, inducing apoptosis, and inhibiting cell growth. A novel noncoding p73 G4C14-to-A4T14 exon 2 polymorphism was associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that p73 G4C14-to-A4T14 polymorphism modulates risk of second primary malignancies (SPM) in patients after index SCCHN. We followed a cohort of 1,384 patients diagnosed with incident SCCHN between May 1995 and January 2007 for SPM development. Log-rank test and Cox proportional hazard models were used to compare SPM-free survival and SPM risk between the different genotype groups. Our results showed that patients carrying the p73 variant AT allele were less likely to develop SPM compared with the patients with p73 GC/GC genotype (Log-rank test, p = 0.013). Compared with the p73 GC/GC genotype, there was a significantly reduced risk of SPM associated with the p73 GC/AT genotype (HR, 0.61, 95% CI, 0.40-0.93) and the combined p73 GC/AT+AT/AT genotypes (HR, 0.59, 95% CI, 0.39-0.89), but a nonsignificantly reduced risk for p73 AT/AT genotype (HR, 0.44, 95% CI, 0.14-1.41). The p73 AT allele was significantly associated with risk of SPM in an allele dose-response manner (p = 0.011 for trend). The risk of SPM associated with p73 variant genotypes (GC/AT+AT/AT) was more pronounced in several subgroups (e.g., older patients, men, minorities, ever smokers, and ever drinkers). Our results support that this p73 polymorphism may be a marker for risk of SPM among patients with an incident SCCHN.

Authors

Li, F; Sturgis, EM; Zafereo, ME; Liu, Z; Wang, L-E; Wei, Q; Li, G

MLA Citation

Li, F, Sturgis, EM, Zafereo, ME, Liu, Z, Wang, L-E, Wei, Q, and Li, G. "p73 G4C14-to-A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck." International journal of cancer 125.11 (December 2009): 2660-2665.

PMID

19585505

Source

epmc

Published In

International Journal of Cancer

Volume

125

Issue

11

Publish Date

2009

Start Page

2660

End Page

2665

DOI

10.1002/ijc.24570

Fas-associated phosphatase-1 is encoded by the protein tyrosine phosphatase, non-receptor type 13 (PTPN13) gene and attributes to the resistance to Fas-mediated apoptosis in several tumors, including squamous cell carcinoma of the head and neck (SCCHN). However, no epidemiological studies have investigated the roles of PTPN13 polymorphisms in SCCHN risk. In this hospital-based case-control study of 1069 SCCHN patients and 1102 non-Hispanic white cancer-free controls, we evaluated the associations between three single-nucleotide polymorphisms c.4068 T>G F1356L (rs10033029), c.4566 A>G I1522M (rs2230600) and c.6241 T>G Y2081D (rs989902) located in the coding region of PTPN13 and SCCHN risk. We found that a significantly increased SCCHN risk was associated with the c.4566 I1522M GG genotype [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.27-2.79] and c.6241 Y2081D GT genotype (OR, 1.26; 95% CI, 1.03-1.53) compared with the c.4566 I1522M AA and c.6241 Y2081D TT genotypes, respectively. Further stratified analyses showed that risk associated with the c.4566 I1522M GG genotype was more profound in the subgroups of young (< or = 57 years), males, never smokers, current drinkers and patients with pharyngeal cancer; that risk associated with c.6241 Y2081D GT genotype persisted in subgroups of old (>57 years), males, current drinkers and patients with pharyngeal and laryngeal cancers and that risk associated with c.6241 Y2081D GG genotype was borderline in patients with laryngeal cancer. In conclusion, polymorphisms in the PTPN13 coding region may be biomarkers for susceptibility to SCCHN in USA populations.

Authors

Niu, J; Huang, Y-J; Wang, L-E; Sturgis, EM; Wei, Q

MLA Citation

Niu, J, Huang, Y-J, Wang, L-E, Sturgis, EM, and Wei, Q. "Genetic polymorphisms in the PTPN13 gene and risk of squamous cell carcinoma of head and neck." Carcinogenesis 30.12 (December 2009): 2053-2058.

PMID

19892796

Source

epmc

Published In

Carcinogenesis

Volume

30

Issue

12

Publish Date

2009

Start Page

2053

End Page

2058

DOI

10.1093/carcin/bgp265

Both TGF-beta1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the TGFB1 and VEGF genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population.The risk associated with genotypes and haplotypes of four TGFB1 SNPs and four VEGF SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity.Compared with the VEGF-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other TGFB1 and VEGF SNPs was associated with risk of gastric cancer.Our data suggested that the VEGF-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.

Authors

Guan, X; Zhao, H; Niu, J; Tang, D; Ajani, JA; Wei, Q

MLA Citation

Guan, X, Zhao, H, Niu, J, Tang, D, Ajani, JA, and Wei, Q. "The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer." BMC gastroenterology 9 (October 16, 2009): 77-.

PMID

19835575

Source

epmc

Published In

BMC Gastroenterology

Volume

9

Publish Date

2009

Start Page

77

DOI

10.1186/1471-230x-9-77

PIN1, a new peptidyl-prolyl cis/trans isomerase, regulates the conformation of Pro-directed phosphorylation sites, revealing a new postphosphorylation regulatory mechanism. PIN1-induced conformational changes potentiate multiple oncogenic signaling pathways, and PIN1 overexpression is reported as a prevalent and specific event in human cancers. In this study, we tested the hypothesis that common polymorphisms in the coding and promoter regions of PIN1 are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We genotyped three selected PIN1 polymorphisms (-842G>C, -667T>C and Gln33Gln) in a hospital-based case-control study of 1006 patients with SCCHN and 1007 cancer-free control subjects. We found that the -842C variant genotypes were associated with decreased risk for SCCHN [Odds Ratio (OR) = 0.74; 95% confidence interval (CI) = 0.59-0.93 for the CG genotype, OR = 0.82; 95% CI = 0.34-2.01 for the CC genotype and OR = 0.74; 95% CI = 0.59-0.93 for CG+CC genotypes, compared with the GG genotype]. However, no altered risks were observed for -667T>C and Gln33Gln polymorphisms. Further experiments of the reporter gene expression driven by the allelic PIN1 promoter showed that the -842G allele had a higher activity than that driven by the -842C allele, suggesting that the -842C allele was associated with a reduced transcriptional activity, a finding consistent with a reduced risk observed in the case-control analysis. Large prospective studies of diverse ethnic groups and diverse cancer sites are warranted to validate our findings.

Authors

Lu, J; Hu, Z; Wei, S; Wang, L-E; Liu, Z; El-Naggar, AK; Sturgis, EM; Wei, Q

MLA Citation

Lu, J, Hu, Z, Wei, S, Wang, L-E, Liu, Z, El-Naggar, AK, Sturgis, EM, and Wei, Q. "A novel functional variant (-842G>C) in the PIN1 promoter contributes to decreased risk of squamous cell carcinoma of the head and neck by diminishing the promoter activity." Carcinogenesis 30.10 (October 2009): 1717-1721.

PMID

19625347

Source

epmc

Published In

Carcinogenesis

Volume

30

Issue

10

Publish Date

2009

Start Page

1717

End Page

1721

DOI

10.1093/carcin/bgp171

PURPOSE: MicroRNAs regulate gene expression by binding to the 3'-untranslated region (UTR) of target genes. Single-nucleotide polymorphisms of critical genes may affect their regulation by microRNAs. We have identified a single-nucleotide polymorphism within the miR-502 seed binding region in the 3'-UTR of the SET8 gene. SET8 methylates TP53 and regulates genome stability. We investigated the role of this SET8 single-nucleotide polymorphism and in concert with the TP53 codon 72 single-nucleotide polymorphism in the propensity for onset of breast cancer. EXPERIMENTAL DESIGN: We measured the SET8 single-nucleotide polymorphisms in a case-control study on 1,110 breast cancer cases and 1,097 controls. RESULTS: The SET8 CC and TP53 GG genotypes were independently associated with an earlier age of breast cancer onset in an allele-dose-dependent manner (for SET8, 52.2 years for TT, 51.4 for TC, and 49.5 for CC; and for TP53, 53.1 years for CC, 51.5 for GC, 50.7 for GG). Individuals with combined SET8 CC and TP53 GG genotypes developed cancer at a median age of 47.7 years as compared with 54.6 years for individuals with combined SET8 TT and TP53 CC genotypes. In the 51 breast cancer tissue samples tested, the SET8 CC genotype was associated with reduced SET8, but not miR-502, transcript levels. CONCLUSIONS: These data suggest that the miR-502-binding site single-nucleotide polymorphism in the 3'-UTR of SET8 modulates SET8 expression and contributes to the early development of breast cancer, either independently or together with the TP53 codon 72 single-nucleotide polymorphism. Larger studies with multiethnic groups are warranted to validate our findings.

Authors

Song, F; Zheng, H; Liu, B; Wei, S; Dai, H; Zhang, L; Calin, GA; Hao, X; Wei, Q; Zhang, W; Chen, K

MLA Citation

Song, F, Zheng, H, Liu, B, Wei, S, Dai, H, Zhang, L, Calin, GA, Hao, X, Wei, Q, Zhang, W, and Chen, K. "An miR-502-binding site single-nucleotide polymorphism in the 3'-untranslated region of the SET8 gene is associated with early age of breast cancer onset." Clinical cancer research : an official journal of the American Association for Cancer Research 15.19 (October 2009): 6292-6300.

PMID

19789321

Source

epmc

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

Volume

15

Issue

19

Publish Date

2009

Start Page

6292

End Page

6300

DOI

10.1158/1078-0432.ccr-09-0826

Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein that possesses both DNA-repair and redox regulatory activities. Although it was originally identified as a DNA-repair enzyme, accumulating evidence supports a role of APE1/Ref-1 in tumor development. To investigate association between APE1/Ref-1 polymorphisms and lung cancer risk in Chinese populations, we first genotyped three variants of APE1/Ref-1 and found a -141 T-to-G variant (rs1760944) in the promoter associated with decreased risk of lung cancer [odds ratio (OR) = 0.62 for GG; P=0.043]. Similar results were obtained in a follow-up replication study. Combined data from the two studies comprising a total of 1072 lung cancer patients and 1064 cancer-free control participants generated a more significant association (P=0.002). We observed lower APE1/Ref-1 mRNA levels in the presence of the protective G allele in human peripheral blood mononuclear cells and normal lung tissues. The -141G-allele-promoter construct exhibited decreased luciferase reporter gene expression. Electrophoretic mobility shift assays and surface plasmon resonance analysis showed that the -141G allele impaired the binding affinity of some transcription factor, accounting for lower APE1/Ref-1-promoter activity. Supershift assays further revealed that the protein of interest was octamer-binding transcription factor-1 (Oct-1). Chromatin immunoprecipitation reconfirmed binding of Oct-1 to the APE1/Ref-1 -141-promoter region. We also found that Oct-1 conferred attenuated transactivation capacity toward the -141G variant by exogenously introducing Oct-1. These data indicate that genetic variations in APE1/Ref-1 may modify susceptibility to lung cancer and provide new insights into an unexpected effect of APE1/Ref-1 on lung carcinogenesis.

Authors

Lu, J; Zhang, S; Chen, D; Wang, H; Wu, W; Wang, X; Lei, Y; Wang, J; Qian, J; Fan, W; Hu, Z; Jin, L; Shen, H; Huang, W; Wei, Q; Lu, D

MLA Citation

Lu, J, Zhang, S, Chen, D, Wang, H, Wu, W, Wang, X, Lei, Y, Wang, J, Qian, J, Fan, W, Hu, Z, Jin, L, Shen, H, Huang, W, Wei, Q, and Lu, D. "Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23.10 (October 2009): 3459-3469.

PMID

19541747

Source

epmc

Published In

The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Volume

23

Issue

10

Publish Date

2009

Start Page

3459

End Page

3469

DOI

10.1096/fj.09-136549

Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.

Authors

Lubin, JH; Purdue, M; Kelsey, K; Zhang, Z-F; Winn, D; Wei, Q; Talamini, R; Szeszenia-Dabrowska, N; Sturgis, EM; Smith, E; Shangina, O; Schwartz, SM; Rudnai, P; Neto, JE; Muscat, J; Morgenstern, H; Menezes, A; Matos, E; Mates, IN; Lissowska, J; Levi, F; Lazarus, P; La Vecchia, C; Koifman, S; Herrero, R; Franceschi, S; Wünsch-Filho, V; Fernandez, L; Fabianova, E; Daudt, AW; Maso, LD; Curado, MP; Chen, C; Castellsague, X; Brennan, P; Boffetta, P; Hashibe, M; Hayes, RB

MLA Citation

Lubin, JH, Purdue, M, Kelsey, K, Zhang, Z-F, Winn, D, Wei, Q, Talamini, R, Szeszenia-Dabrowska, N, Sturgis, EM, Smith, E, Shangina, O, Schwartz, SM, Rudnai, P, Neto, JE, Muscat, J, Morgenstern, H, Menezes, A, Matos, E, Mates, IN, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Franceschi, S, Wünsch-Filho, V, Fernandez, L, Fabianova, E, Daudt, AW, Maso, LD, Curado, MP, Chen, C, Castellsague, X, Brennan, P, Boffetta, P, Hashibe, M, and Hayes, RB. "Total exposure and exposure rate effects for alcohol and smoking and risk of head and neck cancer: a pooled analysis of case-control studies." American journal of epidemiology 170.8 (October 2009): 937-947.

PMID

19745021

Source

epmc

Published In

American Journal of Epidemiology

Volume

170

Issue

8

Publish Date

2009

Start Page

937

End Page

947

DOI

10.1093/aje/kwp222

It is unknown whether population-level racial or ethnic disparities in mortality from squamous cell carcinoma of the head and neck (SCCHN) also occur in the setting of standardized multidisciplinary-team directed care. Therefore, we conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a difference in survival exists for African American or Hispanic American compared with non-Hispanic white American SCCHN patients receiving similar care. Matched pairs were 81 African American case and 81 non-Hispanic white control patients and 100 Hispanic American cases and 100 matched non-Hispanic white controls selected from 1,833 patients of a prospective epidemiologic study of incident SCCHN within a single, large multidisciplinary cancer center. Matching variables included age (+/-10 years), sex, smoking status (never versus ever), site, tumor stage (T(1-2) versus T(3-4)), nodal status (negative versus positive), and treatment. Cases and controls were not significantly different in proportions of comorbidity score, alcohol use, subsite distribution, overall stage, or tumor grade. Matched-pair and log-rank analyses showed no significant differences between cases and controls in recurrence-free, disease-specific, or overall survival. Site-specific analyses suggested that more aggressive oropharyngeal cancers occurred more frequently in minority than in non-Hispanic white patients. We conclude that minority and non-Hispanic white SCCHN patients receiving similar multidisciplinary-team directed care at a tertiary cancer center have similar survival results overall. These results encourage reducing health disparities in SCCHN through public-health efforts to improve access to multidisciplinary oncologic care (and to preventive measures) and through individual clinician efforts to make the best multidisciplinary cancer treatment choices available for their minority patients. The subgroup finding suggests a biologically based racial/ethnic disparity among oropharyngeal patients and that prevention and treatment strategies should be tailored to different populations of these patients.

Authors

Chen, LM; Li, G; Reitzel, LR; Pytynia, KB; Zafereo, ME; Wei, Q; Sturgis, EM

MLA Citation

Chen, LM, Li, G, Reitzel, LR, Pytynia, KB, Zafereo, ME, Wei, Q, and Sturgis, EM. "Matched-pair analysis of race or ethnicity in outcomes of head and neck cancer patients receiving similar multidisciplinary care." Cancer prevention research (Philadelphia, Pa.) 2.9 (September 8, 2009): 782-791.

PMID

19737985

Source

epmc

Published In

Cancer Prevention Research

Volume

2

Issue

9

Publish Date

2009

Start Page

782

End Page

791

DOI

10.1158/1940-6207.capr-09-0154

© 2006 by Oxford University Press, Inc. All rights reserved. This chapter provides an update on the epidemiology of lung cancer with an emphasis on the rapidly expanding literature exploring host susceptibility to tobacco carcinogenesis. It also reviews chemoprevention and lung screening trials.

Authors

Spitz, MR; Wu, X; Wilkinson, A; Wei, Q

MLA Citation

Spitz, MR, Wu, X, Wilkinson, A, and Wei, Q. "Cancer of the Lung." (September 1, 2009). (Chapter)

Source

scopus

Publish Date

2009

DOI

10.1093/acprof:oso/9780195149616.003.0033

Lung cancer leads all other cancers in both incidence and mortality. Recent advances in underlying molecular pathogenesis have validated a panel of protein tyrosine kinases as new targets in lung cancer treatment. Insulin-like growth factor-1 receptor (IGF-1R) is an important tyrosine kinase receptor involved in cell proliferation, differentiation, metabolism, apoptosis, and angiogenesis. Aberrant activation of IGF-1R is frequently found in patients with lung cancer and contributes to malignant transformation and poor prognosis for patients with lung cancer. In this review, we focused on recent progress in the research of IGF-1R's role in lung cancer development and progression, including its structure and biological function, potential mechanisms of aberrant activation, and related oncogenic effects. We also discussed effective IGF-1R antagonists that are currently registered for clinic trials or are undergoing preclinical study with special emphasis on their antibodies and small molecule tyrosine kinase inhibitors.

Authors

Yin, M; Guan, X; Liao, Z; Wei, Q

MLA Citation

Yin, M, Guan, X, Liao, Z, and Wei, Q. "Insulin-like growth factor-1 receptor-targeted therapy for non-small cell lung cancer: A mini review." American Journal of Translational Research 1.2 (August 4, 2009): 101-114. (Review)

Source

scopus

Published In

American Journal of Translational Research

Volume

1

Issue

2

Publish Date

2009

Start Page

101

End Page

114