Cancer incidence in BRCA1 mutation carriers

This study was conducted to determine whether carriers of the BRCA1 gene are also at increased risk of developing cancers other than carcinoma of the breast and ovary. A total of 11,847 individual members, male and female, of 699 families identified in the Breast Cancer Linkage Consortium from North America and Western Europe were studied. The numbers and types of cancers found in this cohort were compared with the expected population incidence rates. Male carriers of the BRCA1 gene were found to have an overall cancer rate similar to the expected risk excluding breast cancer. In contrast, female carriers were found to have a significantly increased risk for all cancers other than breast and ovary (relative risk [RR] = 2.3, 95% CI = 1.93-2.75, P = .001). For all carriers of the BRCA1 mutation, significantly increased risks were found for cancers of the colon, liver, pancreas, uterus, cervix, and other cancers. There were 65 "other cancers"; approximately 20% (N = 12) of these occurred in tested carriers, and the rest occurred in untested relatives of known carriers. Although the expected number of other cancers among women in the cohort was 8.6, the actual number was 47 (RR = 9.64, 95% CI = 6.36-14.61, P <.001). Peritoneal cancer was the most frequent of the "other" cancers, followed by unspecified abdomen or intestinal tract cancers and cancers of other female genital organs. In this group, there was no difference in the relative risk according to age. No increased risk for other cancers was seen in men. The expected incidence of pancreatic cancer and of cancer of the fallopian tube was not known for all populations; but the incidence was estimated on the basis of actual numbers from smaller population groups. There was a significantly increased risk for these cancers (RR = 44.64, 95% CI = 24.86-80.15, P <.001 for pancreas; RR = 49.94, 95% CI = 22.48-110.94, P <.001 for fallopian tube). The overall risk for all cancers was higher for those less than 65 years of age. For those older than 65, there was no difference in the actual rate and the expected rate in either sex. For men, the risk was not increased for those of any age. However, female carriers of the BRCA1 gene who were less than 65 had an overall increased risk of cancer ((RR = 2.62, 95% CI = 2.15-3.18, P <.001). For younger women the risk of pancreatic cancer was 3.10 (95% CI = 1.43-6.70, P =.008), for cervical cancer the risk was 3.84 (95% CI = 2.33-6.33, P <.001), and for uterine cancer the relative risk was 3.40 (95% CI = 2.13-5.44, P <.001). When BRCA1 carriers in North America and Western Europe were compared, the overall RR was higher for European females (RR = 2.91, 95% CI = 2.32-3.66, P <.001). Likewise, Western European female, but not male, noncarriers had a statistically significant elevated risk of overall cancer compared with North Americans (RR = 1.36, 95% CI = 1.09-1.98). European women were at significantly greater risk for uterine cancer, and North American women had a greater risk for cancer of the cervix. The difference was significant for North American women who did not carry the BRCA1 gene. European men less than 65 years of age were significantly more likely to develop prostate cancer than their North American counterparts (RR = 2.53, 95% CI = 1.10-5.82, P =.026). There were no other statistically significant differences seen for men.