Research Interests:
The pathophysiology of cancer reflects the interaction of genetic and environmental factors. Dr. Sellers has been using the tools of epidemiology and molecular genetics to sort out this complex interplay as a means to inform better methods for prevention. Several ongoing studies serve as sources of data for these investigations, including a program project grant of 12,000 women in 426 multigeneration breast cancer families, a cohort of women who received a bilateral or unilateral mastectomy to lower risk, a large case-control study of epithelial ovarian cancer, and a prospective cohort study of over 40,000 postmenopausal women who have been monitored since 1986 to identify dietary, anthropometric, and other lifestyle risk factors for cancer.
A major focus has been the role of folate in reducing breast cancer risk. Dr. Sellers and his colleagues have observed that adequate intake of folate reduces the risk of breast cancer from use of alcohol, that the risk reduction appears predominantly for estrogen recfolate levels are positively correlated with improved survival rates.
The work of Dr. Sellers and his colleagues on familial cancer has sought to understand why, in some families with an inherited predisposition, some women develop breast cancer in their 70s and others in their 20s, while some mutation carriers never develop cancer at all. They have shown that smoking and use of high-estrogen-dose oral contraceptives exacerbate familial risk, but correlates of endogenous estrogen exposure do not. Recent examination of the risk of prostate cancer among relatives of breast cancer patients failed to identify any striking association. Several interesting genetic modifiers are currently being studied in the laboratory and applied to the population.
Dr. Sellers and his colleagues also are working to understand the genetic and nongenetic factors that influence mammographic breast density, a strong risk factor for breast cancer. Dr. Seller's group provided the first evidence for an inherited component of this trait and is conducting a genome screen to identify chromosomal regions that may harbor a gene (or genes) that influence breast density. Hormone replacement therapy has a significant influence on breast density for a subset of the population, and the researchers are working to identify the genetic basis underlying thatphenomenon. This research has the potential to lead to ways to target prescription of hormone replacement therapies such that risks of breast and other cancers are not increased.