Women from families with multiple cases of breast or ovarian cancer are at high risk of developing cancer, and are increasingly concerned about how they may reduce this risk. The BRCA1 gene on chromosome 17q is responsible for cancer susceptibility in most families with the breast- ovarian cancer syndrome and about one-half of families with early-onset familial breast cancer. It is the goal of this study to identify women who carry BRCA1 gene mutations from families who present for genetic counseling and to evaluate current methods of cancer prevention and detection. Carriers will be identified using chromosome 17 markers and linkage analysis. Over 30 families with hereditary breast and breast- ovarian cancer have been identified in the family cancer clinics of Creighton University and McGill University. Through collaborations with other groups and performing linkage-based genetic risk assessment, over 100 currently healthy women with BRCA1 mutations have been identified. The lifetime risk of breast cancer exceeds 80% in carriers of the BRCA1 mutation. For those women from families with ovarian cancer as well, the risk for ovarian cancer among carrier is roughly 50%. This cohort of carriers will be studied to determine the relative effectiveness of the current prevention and management alternatives for high risk women. The screening and surgical experience of each woman in the cohort and the incident cancers and the cancer deaths will be documented. The results of this prospective study will provide specific estimates of incidence and mortality rates of breast and ovarian cancer among BRCA1 carrier women who elect to have prophylactic surgical mastectomy or oophorectomy and those who choose close surveillance. The modifying effect of hormonal co-factors, inducing oral contraceptives and hormone replacement therapy on cancer incidence will also be measured. A case-control study of affected and non-affected carriers will also be carried out using the initial data set to evaluate surgical and hormonal factors.
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