OVARIAN CANCER RISK AND SURVIVAL IN BRCA CARRIERS

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The goal of this K07 Career Award training is to acquire expertise in the requisite disciplines for molecular and genetic cancer epidemiology research, with an emphasis on femal cancers. Two interlocking areas of study will be pursued. First, a series of independent studies, laboratory projects and seminars/conferences will provide an understanding of the laboratory techniques employed in genetic epidemiology studies, the underlying biology of female cancers, and the clinical relevance of genetic epidemiology research. Second, studies in epidemiology and biostatistics will ensure the development of study design, management and analysis skills. The cornerstone of this training will be a study investigating ovarian cancer risks and survival among BRCA1/2 mutation carriers. Because the case fatality rate of ovarian cancer is so high, many doctors advise these high-risk women to engage in the two behaviors that most strongly prevent ovarian cancer: using oral contraceptives (Ocs) and bearing more children. While one recent study did find Ocs to be protective for BRCA1/2 carriers, concerns about the study's design question its validity. Moreover, one report suggests that for BRCA1/2 mutation carriers, OC use substantially increases breast cancer risk. Another study suggests that having more children increases (rather than decreases) ovarian cancer risk in these women. There are also contradictory findings on the survival of BRCA1/2-associated ovarian cancer patients. Therefore, a well-designed study investigating the effect of OC use and parity on ovarian cancer risk and survival in BRCA1/2 carriers is urgently needed. We will use a case-only study to determine the protectiveness of Ocs and parity against ovarian cancer among women carrying BRCA1/2 mutations versus among women not carrying these mutations, and we will determine whether there is a survival difference between the two groups. We will obtain BRCA1/2 mutation status from banked tissue specimens of about 400 Ashkenazi Jewish women with ovarian cancer identified from tumor registries in Pennsylvania, Ohio, New York and Florida or who participated in an NIH-sponsored study. We will link these results to information on OC use and parity. The protection afforded by OC use and parity will then be compared among BRCA1/2 mutation carriers versus among non-carriers. Survival status will be obtained from the National Death Index and the differences in survival between the two groups will be compared. The information from this study will have immediate implications for clinical practice and for the design of clinical trials. Additionally, this training will provide the skills and experience needed to become an independent researcher in the molecular and genetic epidemiology of female cancers.