Grant Number:	1R03CA106079-01 Interpret this number
Primary Investigator:	Terry, Kathryn
Organization:	Brigham And Women'S Hosp., Inc.
Project Title:	Genetic Variants of Hormone Receptors in Ovarian Cancer
Fiscal Year:	2003

DESCRIPTION (provided by applicant): Epidemiologic and in vitro data suggest a role for reproductive hormones in ovarian cancer development. The tissue specific effect of these hormones is controlled by the expression of hormone receptors. Normal ovarian epithelium contains both estrogen and progesterone receptors. Animal models and cell lines demonstrate that estrogen increases ovarian epithelial proliferation and induce ovarian tumors, whereas, progesterone inhibits growth and increases apoptosis of the ovarian epithelium. In addition, epidemiologic literature suggests a protective effect for the combination of estrogen and progesterone in oral contraceptives, which are consistently protective. Unopposed estrogen in the form of menopausal therapy appears to increase ovarian caner risk but formulations with estrogen and progesterone have no consistent relationship with ovarian cancer. Our goal is to examine the effect of genetic variation in hormone receptors on the risk of ovarian cancer, using a New England based case-control study. Specifically, this study will test whether common haplotypes of estrogen receptor genes (estrogen receptor alpha and estrogen receptor beta) or the progesterone receptor gene are associated with an increased risk of ovarian cancer. In addition, this study will test whether the association between a functional polymorphism in the progesterone receptor, +331 G/A, increases ovarian cancer risk. Variables such as parity, menopausal status, body mass index, and exogenous hormones affect estrogen and progesterone levels, therefore, interaction with these variables will be considered. Ovarian cancer is particularly deadly due to its asymptomatic progression and poor prognosis at late stages of disease. Advances in prevention and detection may come from a better understanding of the genetic determinants of ovarian cancer, which might inform decisions about lifestyle modifications that could lower risk.





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