biostudies-literatureAntoniou ANCI NIH HHS1117-30https://www.ebi.ac.uk/biostudies/studies/S-EPMC1180265biostudies-literatureUnknown72(5)Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence American journal of human geneticsAverage risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.PMC1180265R01 CA63682R01 CA0636821R01 CA81203Anton-Culver HOlsson HEerola HLubinski JThorlacius SPharoah PDThompson DAntoniou ARadice PTang NPasini BGronwald JEvans DGEaston DFLalloo FGorski BTulinius HNarod SKallioniemi OPOlah EEccles DMEvans CSyrjakoski KJohannsson OWarner EBorg AManoukian SHopper JLNevanlinna HPeto JLoman NRisch HAEyfjord JEfalseAverage risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence 2003-01-01T00:00:00Z2003 May2025-04-04T21:07:22.111Z2019-03-27T01:09:09ZS-EPMC11802651267755810.1086/375033