Qingyi Wei

Smoking and alcohol exposure continue to be the dominant risk factors for the development of head and neck squamous cell carcinoma (SCCHN) worldwide. Moreover, human papillomavirus (HPV) is associated with SCCHN, particularly SCC of the oropharynx (SCCOP). Body mass index (BMI) has been reported as a possible risk factor for SCCHN, yet the data available so far about the relationship between BMI and SCCHN risk have been mixed. We sought to clarify this relationship. BMI and demographic, clinical, and epidemiological information at diagnosis were collected from 2310 SCCHN cases and 1915 controls (who were cancer-free) from October 2001 through May 2013. The odds ratios (ORs) and 95 percent confidence intervals (95% CI) were determined using the logistic regression process. Multivariable models were used to evaluate the strength of the relation between BMI and SCCHN risk. At diagnosis, 64 (2.8%) of the cases were underweight (BMI <18.5 kg/m2), 661 (28.6%) were normal weight (BMI 18.5<25 kg/m2), 833 (36.1%) were overweight (BMI 25<30 kg/m2), and 752 (32.6%) were obese (BMI ≥30 kg/m2). Comparatively, the ORs (95% CIs) for SCCHN associated with being underweight, overweight, and obese were 2.6 (1.54.7), 0.7 (0.6-0.8), and 0.8 (0.7-0.9), respectively, after adjusting for age, gender, race/ethnicity, smoking, and alcohol consumption. On analysis stratified by tumor sites, the risk of SCCOP among patients seropositive for HPVE6 and/or HPVE7 was higher among the overweight (OR, 5.4, 95% CI, 1.3-23.1) and obese patients (OR, 2.4, 95% CI, 1.1-7.6) compared to the normal weight patients. These findings suggest that pretreatment BMI could be a major risk factor for SCCHN, and the association between BMI and HPV may increase the risk of SCCOP.

Both in vivo and in vitro evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown. METHODS: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients. RESULTS: we identified two SNPs (EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, P=0.001) and 1.66 (1.22-2.26, P=0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets (P trend<0.001 and 0.002, respectively). Additional functional analysis revealed that both EML1 rs10151787 G and HIST1H4E rs2069018 C alleles were associated with elevated mRNA expression levels in normal tissues. CONCLUSIONS: Our findings suggest that EML1 rs10151787 A>G and HIST1H4E rs2069018 T>C are independent prognostic biomarkers for CMSS.

Background: Single nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage. Methods: DNA extracted from normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients. Results: We identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P > 0.05). Conclusions: SNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.

Accumulating evidence supports a role of various damage-associated molecular patterns (DAMPs) in progression of lung cancer, but roles of genetic variants of the DAMPs-related pathway genes in lung cancer survival remain unknown. We investigated associations of 18,588 single-nucleotide polymorphisms (SNPs) in 195 DAMPs-related pathway genes with non-small cell lung cancer (NSCLC) survival in a subset of genotyping data for 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another independent subset of genotyping data for 984 patients from Harvard Lung Cancer Susceptibility Study. We performed multivariate Cox proportional hazards regression analysis, followed by expression quantitative trait loci (eQTL) analysis, Kaplan-Meier survival analysis and bioinformatics functional prediction. We identified that two SNPs (i.e., CLEC4E rs10841847 G>A and BIRC3 rs11225211 G>A) were independently associated with NSCLC overall survival, with adjusted allelic hazards ratios of 0.89 (95% confidence interval=0.82-0.95 and P=0.001) and 0.82 (0.73-0.91 and P=0.0003), respectively; so were their combined predictive alleles from discovery and replication datasets (P trend=0.0002 for overall survival). We also found that the CLEC4E rs10841847 A allele was associated with elevated mRNA expression levels in normal lymphoblastoid cells and whole blood cells, while the BIRC3 rs11225211 A allele was associated with increased mRNA expression levels in normal lung tissues. Collectively, these findings indicated that genetic variants of CLEC4E and BIRC3 in the DAMPs-related pathway genes were associated with NSCLC survival, likely by regulating the mRNA expression of the corresponding genes.