Cancer Risk, Detection and Interception (CRDI)
Research in the Cancer Risk, Detection, and Interception (CRDI) Program spans the continuum of basic, population, clinical, and translational research. Strengths include complementary approaches spanning cancer epidemiology, exposures, and genetics, to promote early intervention and avoid cancer progression. Collectively, CRDI Program Members seek to drive discovery and advances in novel biomarker identification, risk assessment strategies, early detection, and cancer interception.
Globally, the CRDI Program seeks to provide the infrastructure and opportunities to facilitate collaborative research among CRDI members and across the Duke Cancer Institute. Through these collaborations, CRDI members aim to disseminate new knowledge and reduce the burden of cancer both regionally and beyond.
As a theme threaded throughout the work of its members, CRDI seeks to reduce the cancer burden in the Duke Cancer Institute (DCI) catchment area, as well as addressing cancer health disparities locally, regionally, and globally. Our work can also be categorized into two focus areas, as described below.
Focus Area 1: Risk Identification and Assessment (Leader: Heather Stapleton): Research in this area seeks to improve the prevention of cancer and risk stratification through exposure measurement, discovery of novel risk factors for better risk prediction, identification of high-risk individuals for targeted prevention, and studies of genetic predisposition and cancer initiation.
Focus Area 2: Cancer Detection and Interception (Co-Leaders: Shelley Hwang and Evan Myers): Research in this area seeks to expand cancer detection and interception (primary and secondary) through research into chemoprevention, cancer screening, cutting-edge screening technology, and with a focus in situ/early stage disease.
Meira Epplein, PhD, MS, MA, is an epidemiologist specializing in cancer prevention, with a focus on modifiable risk factors, including infection, and health disparities. She has been awarded four grants from the NCI that focus on gaining a greater understanding of the diversity of the bacteria Helicobacter pylori and host response to infection and the association with gastrointestinal cancers. She is committed to supporting transdisciplinary collaboration and training the next generation to further consequential cancer epidemiological research.
Katherine Garman, MD, MHS, is a gastroenterologist and basic/translational scientist focused on the underlying biology associated with carcinogenesis in the upper GI tract. She has NIH funding to study the role of gastrin in esophageal repair and pre-malignant disease as well as the functional significance of genes associated with familial Barrett’s esophagus and esophageal cancer. In partnership with Dr. Epplein, she is co-lead for an NCI-funded P20 project on Helicobacter pylori, gastric intestinal metaplasia and gastric cancer disparities.
This study adapted an ultra-sensitive sequencing platform originally developed to detect mutations arising in bacteria populations to detect de novo mutations in the oncogene KRAS in vivo. Using this assay, it was possible to capture the moment the cancer-causing mutation first occurred in KRAS, helping unravel how cancer first begins, and paving the way for early detection of this disease.
- Li S, MacAlpine DM, Counter CM. Capturing the primordial Kras mutation initiating urethane carcinogenesis. Nat Commun. 2020 Apr 14;11(1):1800. PubMed PMID: 32286309; PubMed Central PMCID: PMC7156420.
Ancestry-related biology is one of the multi-level contributors to cancer health disparities. Comparative genomic studies of tumor tissues from Black and White patients have revealed novel molecular pathways driving tumor aggressiveness and potential target molecules for precision oncology approaches to cancer therapy.
- Robinson TJ, Freedman JA, Al Abo M, Deveaux AE, LaCroix B, Patierno BM, George DJ, Patierno SR. Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities. Clin Cancer Res. 2019 May 15;25(10):2963-2968. PubMed PMID: 30755441; PubMed Central PMCID: PMC6653604
Currently, the vast majority of women diagnosed with pre-invasive breast cancer (DCIS) undergo surgery. Our findings suggest that DCIS patients without locoregional treatment have a limited risk of progression to invasive breast cancer. This in turn implies that there may be overtreatment, especially among older patients and patients with elevated comorbidities.
- Ryser MD, Weaver DL, Zhao F, Worni M, Grimm LJ, Gulati R, Etzioni R, Hyslop T, Lee SJ, Hwang ES. Cancer Outcomes in DCIS Patients Without Locoregional Treatment. J Natl Cancer Inst. 2019 Sep 1;111(9):952-960. PubMed PMID: 30759222; PubMed Central PMCID: PMC6748726.
In this large genome-wide association study for genetic risk of squamous cell carcinoma of the head and neck (SCCHN) among 7376 cases and 7725 cancer-free controls, the investigators identified a few novel genetic variants in human leukocyte antigen loci for oropharyngeal cancer risk, highlighting the importance of immunologic mechanism against human papilloma virus infection in the disease etiology.
- Shete S, Liu H, Wang J, Yu R, Sturgis EM, Li G, Dahlstrom KR, Liu Z, Amos CI, Wei Q. A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck. Cancer Res. 2020 Jun 15;80(12):2451-2460. PubMed PMID: 32276964; PubMed Central PMCID: PMC7299763
This paper, which uses data from the Utah Population Database, demonstrates the importance of cancer family history information in determining prostate cancer risk in unaffected men. Importantly, men with three or more first degree relatives with prostate cancer or those with two or more first or second degree relatives with early-onset prostate cancer (defined as prostate cancer diagnosed <55 yrs) were at very high risk for early-onset disease.
- Beebe-Dimmer JL, Kapron AL, Fraser AM, Smith KR, Cooney KA. Risk of Prostate Cancer Associated With Familial and Hereditary Cancer Syndromes. J Clin Oncol. 2020 Jun 1;38(16):1807-1813. PubMed PMID: 32208047; PubMed Central PMCID: PMC7255976.
Long-term outcomes after colonoscopy screening are relatively uncertain. This study found that baseline screening colonoscopy findings associate with advanced neoplasia within 10 years. To note, individuals with only 1 or 2 small adenomas at baseline have a low risk of advanced neoplasia over 10 years. Alternative surveillance strategies could be considered for these individuals.
- Lieberman D, Sullivan BA, Hauser ER, Qin X, Musselwhite LW, O'Leary MC, Redding TS 4th, Madison AN, Bullard AJ, Thomas R, Sims KJ, Williams CD, Hyslop T, Weiss D, Gupta S, Gellad ZF, Robertson DJ, Provenzale D. Baseline Colonoscopy Findings Associated With 10-Year Outcomes in a Screening Cohort Undergoing Colonoscopy Surveillance. Gastroenterology. 2020 Mar;158(4):862-874.e8. PubMed PMID: 31376388
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