ORAL CONTRACEPTIVES, HORMONAL RISK FACTORS AND BRCA1

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DESCRIPTION (Applicant's Description): Mutations in the breast cancer susceptibility gene BRCA1 may be involved in a substantial number of breast cancers diagnosed at an early age. However, the age at which breast cancer occurs appears to vary substantially, even in women from the same family with the same mutation. Further, recent evidence suggests that breast cancer risk in BRCA1 mutation carriers is much lower than the previously reported 85%. This suggests that other, genetic or nongenetic, factors play a role in whether or when breast cancer occurs in women with a BRCA1 mutation. Epidemiological evidence suggests that oral contraceptive (OC) use at an early age may increase risk of breast cancer. Further, OC use appears to be particularly detrimental in young women with a family history. We have preliminary data suggesting that BRCA1 mutation carriers have a much higher risk associated with OC use than non- carriers. Such a detrimental effect of OC use in BRCA1 mutation carriers could be due to increased breast cell proliferation in these women. Experimental evidence suggests that BRCA1 may be a hormonally induced negative growth regulator. We propose to conduct a population-based study to determine the ratio of relative risk of breast cancer associated with OC use in BRCA1 mutation carriers and the relative risk of breast cancer associated with OC use in non-carriers. This information can subsequently be used to determine the relative risk of breast cancer associated with OC use in BRCA1 mutation carriers. The secondary aims of this study are to determine whether other hormonal risk factors such as selected reproductive factors and physical exercise differentially affect breast cancer risk in BRCA1 mutation carriers and non-carriers. This study will provide valuable epidemiologic information regarding the role of BRCA1 in breast cancer etiology, and could yield important results in developing intervention regimens and appropriate counseling for women with a BRCA1 mutation.