Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers

We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated fami lies from Southern Sweden using data from parish and local tax authorities, as well as the Swedish Cancer Registry, Cause of Death Registry and Census Registry. 150 malignant tumours were analysed from 1145 relatives in the B RCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, t he incidence for all malignant tumours was significantly increased for both BRCA1- standardised morbidity rate, SMR, 1.98, 95% confidence interval (CI ) 1.59-2.45; P<0.0001 and BRCA2- (SMR 1.79, 95% CI 1.35-2.31; P<0.0001) ass ociated family members. For women in BRCA1-associated families, the inciden ce of breast cancer (SMR 3.76, 95% CI 2.29-5.80, P<0.0001), ovarian cancer (SMR 15.49, 95% CI 9.46-23.92, P<0.0001), stomach cancer (SMR 5.86, 95% CI 1.60-15.01, P = 0.005) were significantly increased. Amongst men only invas ive squamous cell cancer of the skin was significantly increased (SMR 6.02, 95% CI 1.96-14.05, P=0.002). In BRCA2 associated families, female breast c ancer (SMR 3.03, 95% CI 1.61-5.18, P=0.0005) was increased after exclusion of index cases. If these were included, ovarian cancer (SMR 5.16, 95% CI 1. 89-11.24, P=0.001), invasive cervical cancer (SMR 4.21, 95% CI 1.15-10.79, P=0.016), male breast cancer (SMR 290.52, 95% CI 125.42-572.43, P<0.0001), and prostate cancer (SMR 2.21, 95% CI 0.89-4.56, P=0.042) were significantl y increased. The increased risk for ovarian cancer in BRCA2 related familie s were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer ty pes do not appear to be greatly increased in BRCA1- and BRCA2-associated fa milies and does not warrant specific clinical follow-up in carriers. (C) 19 99 Elsevier Science Ltd. All rights reserved.