Biological Basis for Chemoprevention of Ovarian Cancer
Final rept. 1 Oct 2002-30 Sep 2006
DUKE UNIV MEDICAL CENTER DURHAM NC
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To achieve a better understanding of the etiology of ovarian cancer 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 950 cases and 950 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of polymorphisms in single genes including most recently the androgen receptor have been performed. We also have performed an Illumina array experiment with 1 536 haplotype tagging single nucleotide polymorphisms in about 150 candidate genes. This data presently is being analyzed. We also have played a leadership role in establishing an international consortium in which groups are working together to validate initial 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 in chickens that incorporates both progestins and vitamin D analogues is near completion. 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