title: Prevalence of recurring BRCA mutations among Ashkenazi Jewish women with breast cancer.
abstract: The BRCA1 mutations 185delAG and 5382insC and the BRCA2 mutation 6174delT have been detected in a significant proportion of Ashkenazi Jewish women with early-onset breast cancer. A group of 236 Jewish women with breast cancer was screened for the presence of these alterations. Mutations were detected in 25.0% (59/236). Among women with breast cancer diagnosed at or before the age of 45, the prevalence of these mutations was 29.1% (42/144). Among women diagnosed with breast cancer after age 45, mutations were noted in 18.5% (17/92). Among women with a family history of breast or ovarian cancer, the likelihood of detecting a mutation was 32.1% (53/165). BRCA1 185delAG was the most common mutation overall (40/236, 16.9%). The ratio of BRCA1 185delAG to BRCA2 6174delT was 4.0 in women with early-onset breast cancer and 1.3 in women with breast cancer diagnosed after age 45. Clinical features such as age at diagnosis, family history of breast or ovarian cancer, bilateral breast cancer, and personal history of breast and ovarian cancer increase the likelihood of detecting mutations among Ashkenazi women with breast cancer. The yield of testing is low in the absence of any of these features.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Robson
authors.forename: M K
authors.initials: MK
authors.lastname: Dabney
authors.forename: G
authors.initials: G
authors.lastname: Rosenthal
authors.forename: S
authors.initials: S
authors.lastname: Ludwig
authors.forename: M H
authors.initials: MH
authors.lastname: Seltzer
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.forename: B
authors.initials: B
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Osborne
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: F
authors.initials: F
authors.lastname: Gilbert
authors.forename: K
authors.initials: K
authors.lastname: Offit
mesh_terms: D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing; D006801:Humans; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors