Ovarian and breast cancer risks to women in families with two or more cases of ovarian cancer.

There are few published estimates of the risk of developing breast or ovarian cancer in women with a strong family history of ovarian cancer. As these women commonly present to family cancer clinics, accurate cancer risk estimates are needed. We have estimated these risks in women from families with 2 or more confirmed ovarian cancers in first-degree relatives using data from the UKCCCR Familial Ovarian Cancer Register. The number of cancers observed in more than 10,000 person years of follow-up was compared with the number expected based on national-, age-, sex- and period-specific incidence rates. The relative risk of ovarian cancer was found to be 7.18 (95% CI 3.82-12.3), declining from 16.0 (6.40-32.9) in women under 50 to 4.38 (1.60-9.52) in women 50 years of age and older. For breast cancer, the relative risk for women under 50 was 3.74 (2.04-6. 28) and 1.79 (1.02-2.90) for women 50 years of age and older (average RR 2.36, 1.59-3.37). These correspond to absolute risks by age 70 of 11% for ovarian cancer and 15% for breast cancer. When the analyses were restricted to families that had been negative for mutations in the breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2, the ovarian cancer risk was 11.59 (3.12-29.7) and that of breast cancer 3.32 (1.52-6.31). As well as having clinical relevance, our finding may suggest that other breast/ovarian cancer genes are segregating in these families, though the possibility of undetected BRCA1/2 mutations must also be considered.