THE GENETIC ATTRIBUTABLE RISK OF BREAST AND OVARIAN-CANCER

BACKGROUND. The age-specific proportion of breast and ovarian cancer i n the general population that is likely to be due to a breast/ovarian cancer susceptibility gene(s) is estimated. In addition, the age-speci fic penetrance of ovarian cancer for women predicted to be carriers of a susceptibility gene is calculated using population-based data. METH ODS. Data are from the Cancer and Steroid Hormone Study, a population- based, case-control study conducted by the Centers for Disease Control , which includes 4730 breast cancer cases aged 20 to 54 years. Informa tion regarding the occurrence of breast and ovarian cancer was collect ed for mothers and sisters of the cases during an in-home interview. T he probability of being a breast cancer susceptibility gene carrier wa s calculated for each of the breast cancer cases using information on the family history of breast cancer. The calculated risk of ovarian ca ncer in the first-degree relatives of breast cancer cases with a high probability of being a gene carrier is compared with that seen in firs t-degree relatives of breast cancer cases with a low probability of be ing a gene carrier and used to calculate the proportion of ovarian can cer cases that are likely to be due to a breast/ovarian susceptibility gene(s) as well as the age-specific risk of developing ovarian cancer for gene carriers. RESULTS. Approximately 10% of ovarian cancer cases and 7% of breast cancer cases in the general population are estimated to be carriers of a breast/ovarian cancer susceptibility gene; these women are found primarily in families characterized by multiple cases of the early onset of breast cancer. The proportion of breast cancer c ases predicted to be attributable to the gene decreases markedly with age; approximately 33% of cases age 20-29 pears compared with approxim ately 2% of cases age 70-79 years. The proportion of ovarian cancer ca ses predicted to be due to the susceptibility gene ranges from 14% amo ng patients diagnosed in their 30s to 7% among those diagnosed in thei r 50s. Carriers are predicted to have at least 15 times the age-specif ic risk of ovarian cancer of noncarriers. Among women predicted to car ry the gene, the cumulative risk of developing ovarian cancer by the a ge of 59 years is approximately 10%. CONCLUSIONS. The estimates provid ed may prove helpful to clinicians until such time as large scale popu lation-based screening for breast and ovarian cancer susceptibility ge nes is possible. (C) 1996 American Cancer Society.