Program Leader: Thomas Rohan, M.D., Ph.D.
Co-Program Leader: Howard Strickler, M.D.
The Cancer Epidemiology Program is organized into three major scientific areas, each related to a particular type of cancer risk factor: (1) Viral - this research focuses on human papillomavirus (HPV) and its role in anogenital and oral cancers. Recent highlights include a report that HPV16 DNA methylation patterns are strongly associated with prevalent and incident detection of cervical precancer, and a study of HPV URR/E6 sequences which found that the continued evolution of HPV types has led to genetic discrimination linked to viral persistence and cancer risk. Host immunity was addressed in several ways. Variation in the gene coding for TAP1 protein, which is essential for assembling HLA class I molecules, was shown to be associated with odds of precancer. In studies of HIV-positive women, the use of highly active anti-retroviral therapy was found to reduce risk of incident and persistent infection by oncogenic HPV, and co-testing for HPV was shown to have a strong negative predictive value for precancer in cytologically normal HIV-positive women. (2) Hormonal/Obesity/Inflammation - research focuses on the role of the insulin/IGF-axis, sex hormones, adipocytokines, and related pathways in obesity-associated cancers (e.g., colon, breast, prostate, etc). Recent highlights include a series of prospective studies that found that insulin (not estrogens) largely explains the relationship between obesity and breast cancer and, for the first time, that endogenous sex hormones are associated with colorectal cancer risk. Insulin and estrogen were both strong predictors of risk of endometrial cancer. In additional studies, use of estrogen hormone replacement therapy increased the risk of benign proliferative breast disease, a condition associated with increased risk of breast cancer. (3) Genetic and Epigenetic research focuses on germline and somatic mutations, genetic polymorphisms, DNA methylation, and microRNAs. Among recent highlights, investigators reported that risk of high grade / aggressive prostate cancer is positively associated with BRCA1/BRCA2 (DNA repair gene) mutations and, in a second study, aggressive prostate cancer was associated with polymorphisms in TCF7L2 – a gene thought to act through the Wnt/beta-catenic signaling pathway. A series of methodologic studies to improve the laboratory and statistical tools for conducting genetic and epigenetic research were reported, including methods to study RNA from paraffin-embedded tissue and novel statistical methods to study gene-gene and gene-environment interactions. Members of this program are also involved in outreach to the African population through the AMC and an NCI-funded (D43) grant to enhance the research capacity for the study of cervical cancer in Rwanda. This relationship was extended with the recent initiation of a clinical trial of chemoradiotherapy in HIV-associated locally advanced cervical cancer in several African countries.
Selected Achievements in the Cancer Epidemiology program