title: Incidence of malignant tumours in relatives of BRCA1 and BRCA2 germline mutation carriers.
abstract: We investigated cancer incidence between 1958 and 1995 in 1873 individuals belonging to 29 consecutively identified BRCA1 and 20 BRCA2 associated families 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 BRCA1 families and 87 tumours were analysed from 728 relatives in the BRCA2 families. After excluding index cases which led to the mutation analysis, the 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) associated family members. For women in BRCA1-associated families, the incidence 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 invasive 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 cancer (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 significantly increased. The increased risk for ovarian cancer in BRCA2 related families were limited to the cases leading to mutation analysis. Our data suggest that apart from breast and ovarian cancer, the incidence of other cancer types do not appear to be greatly increased in BRCA1- and BRCA2-associated families and does not warrant specific clinical follow-up in carriers.
authors.affiliation: Department of Oncology, University Hospital Lund, Sweden. oskar.johannsson@onk.lu.se
authors.forename: O
authors.initials: O
authors.lastname: Johannsson
authors.forename: N
authors.initials: N
authors.lastname: Loman
authors.forename: T
authors.initials: T
authors.lastname: Möller
authors.forename: U
authors.initials: U
authors.lastname: Kristoffersson
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: H
authors.initials: H
authors.lastname: Olsson
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D005190:Family; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D012189:Retrospective Studies; D013548:Sweden / Q000453:epidemiology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors