Biological Basis for Chemoprevention of Ovarian Cancer
Annual rept. 1 Oct 2004-30 Sep 2005
DUKE UNIV MEDICAL CENTER DURHAM NC
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The rationale for ovarian cancer prevention is highlighted by the observations that pregnancy and birth control pill use are strongly protective. To achieve a better understanding of the etiology of ovarian cancer, which can then be translated into effective prevention strategies, we have initiated a case-control study that considers genetic susceptibility, epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 800 cases and 850 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of genetic polymorphisms BRCA12, progesterone receptor, vitamin D receptor, transforming growth factor-beta receptor, BRAF have been performed. In addition to analyses of polymorphism data within the North Carolina Study, we are performing joint analyses with other groups to validate positive associations. An initial ovarian cancer chemoprevention trial with levoneorestrel in chickens demonstrated a protective effect and we have shown that progestin mediated apoptosis in the ovarian epithelium is mediated by transforming growth factor-beta. In vitro data has suggested that vitamin D analogues may also represent appealing chemopreventives. A chemoprevention trial incorporates both progestins and vitamin D analogues is being initiated. These studies have the potential to increase our ability to identify high-risk women and to lead to the development of chemoprevention strategies that might decrease mortality from this disease.
- Anatomy and Physiology
- Medicine and Medical Research