DESCRIPTION (provided by applicant): Lifetime breast cancer risks among carriers of mutations of the genes BRCA1 and BRCA2 have been estimated at 40-80%. Thus some 20-60% of carriers live to advanced ages without developing the disease, which suggests that other genes or personal attributes may modify carriers' risks. At present however, title is known about such personal characteristics. There is urgent need to determine which, if any, modifiable lifestyle characteristics may alter a carrier's risk of developing breast cancer, to assist her in making rational, informed choices about such preventive options as prophylactic mastectomy. We propose to use uniformly collected data from young (aged < 50 years) case (N=425) and control (N=352) carriers of deleterious BRCA1 or BRCA2 mutations to evaluate associations between breast cancer risk and five modifiable characteristics. These are: history of oral contraceptive use, history of diagnostic or therapeutic chest irradiation prior to diagnosis, alcohol consumption, cigarette smoking, and physical activity patterns during puberty, young adulthood and middle age. We will focus on carriers under age 50 years at diagnosis (cases) or interview (controls) who have participated in an international Collaborative Family Registry for Breast Cancer Studies (CFRBCS) and in clinical studies in New York, Ontario and Australia. We will use unconditional logistic regression to estimate odds-ratios relating these attributes to breast cancer risk while controlling for potential confounders, and use robust variance estimators to account for any correlation present in attributes of related carriers. These data on modifiable characteristics from a large group of young carriers of BRCA1 or BRCA2 mutations represent a unique resource for advancing our knowledge about breast cancer prevention in premenopausal women at high risk for the disease. The proposed analysis will provide new information on alternatives to mastectomy as a preventive strategy for these women.
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