In the United States in 1992, there were about 21,000 new cases of cancer of the ovary, and approximately 13,000 women died from it, making it the most lethal of the gynecological malignancies. Over a lifetime, close to 2 percent of women are affected. Ovarian cancer is difficult to treat because patients frequently present late in the course of the disease, which may be asymptomatic until advanced stages. The few established risk factors do not appear to account for a large fraction of disease incidence, and the possible mechanisms by which these factors affect risk of developing ovarian cancer are not well understood. Current work suggests that between 5-10 percent of ovarian cancers are familial. While not all women in families so affected get the disease, they are at greatly increased risk for it, as well as for breast cancer. A population-based study in the province of Ontario, Canada, is thus proposed to ascertain differences in reproductive, lifestyle and other risk factors between genetic and non-genetic cases, and between genetic cases and their unaffected gene-carrying sisters and first-cousins. The fraction of all ovarian-cancer cases in the population that are from families with hereditary ovarian cancer or with the breast-ovarian cancer syndrome will also be estimated. In total, approximately 120 newly-diagnosed genetic cases of epithelial ovarian cancer will be identified over a 4.3-year period, by obtaining pedigree information from all cases occurring in the province during that time. For comparison, 120 unaffected gene-carrying sisters and first-cousins of the cases will be identified, as well as a random sample 260 non-genetic cases of ovarian cancer. All of the subjects will be interviewed by a trained genetic-counselor/interviewer using a standardized structured questionnaire, to ascertain information about ethnicity, education, various medical conditions, lifestyle factors, and an extensive description of menstrual characteristics, pregnancies, hormone and contraception usage, and infertility factors. For use in the genetic linkage analyses, pedigree information and blood samples will be obtained from subjects and members of their extended families, along with hospital pathology reports for family members identified as having had ovarian or breast cancer. Paraffin-embedded tissue blocks will be recovered for many of the deceased family members who had ovarian or breast cancer. The blood samples and paraffin blocks will be used to test for five genetic markers surrounding BRCA1, the breast-ovarian cancer susceptibility gene, located on chromosome 17. Because this study will identify individuals at high risk of breast or ovarian cancer, all women in this study (and their family members) will be invited to attend without charge the Familial Ovarian Cancer Clinic at Toronto General Hospital, for screening, counseling and continued follow-up. This project is performed in collaboration with another on the natural history of BRCA1 carriers, and a third on the molecular epidemiology of breast cancer.
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