title: Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women with sporadic compared with familial early onset breast cancer.
abstract: To delineate the clinical, genetic and family history attributes in Jewish Ashkenazi women with early onset (< 42 years) breast cancer we genotyped such women for the three predominant Jewish Ashkenazi mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT). The study cohort was composed of 172 women diagnosed with breast cancer at or before the age of 42 years, obtained from the oncology department registry. Mutations were identified in 54 women (31%). Of 79 women with a positive family history for breast and/or ovarian cancer, and 93 with no such family history, 45 (57%) and 9 (10%), respectively, were mutation carriers (chi2 = 46; P < 0.001). Contralateral breast cancer occurred in 15 of 54 mutation carriers (28%) compared with 8 of 118 (7%) non-carriers (chi2= 14; P < 0.001). Early onset breast cancer per se is a weak predictor of finding germ line mutation(s) in BRCA1 and BRCA2, unless associated with a positive family history and/or bilaterality.
authors.affiliation: Department of Human Genetics, Rambam Medical Center, Haifa, Israel. rgershoni@rambam.health.gov.il
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: E
authors.initials: E
authors.lastname: Dagan
authors.forename: G
authors.initials: G
authors.lastname: Fried
authors.forename: R
authors.initials: R
authors.lastname: Bruchim Bar-Sade
authors.forename: R
authors.initials: R
authors.lastname: Sverdlov-Shiri
authors.forename: G
authors.initials: G
authors.lastname: Zelicksson
authors.forename: E
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics*; D016015:Logistic Models; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D012189:Retrospective Studies; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors