title: BRCA1 variants in a family study of African-American and Latina women.
abstract: We sequenced the entire coding region of BRCA1 to improve our understanding of the frequency and nature of BRCA1 variants in African-American and Latina women identified from a multiethnic cohort in Los Angeles, California. The study included 109 African-American and 140 Latina sibships from families with two or more cases of breast or ovarian cancer among first-degree relatives. BRCA1 was sequenced in 278 breast or ovarian cancer cases and 229 unaffected sisters. The proportion of cases with known disease-causing mutations was low (0.72, 95% confidence interval: 0-1.7%). In total, 33 sequence variants were identified, including two protein truncation mutations, one deletion, and six silent and 24 missense variants. Two novel rare variants were identified that appeared to act as benign polymorphisms. Four rare variants may be unique to women of African descent based on existing literature, and three have been described exclusively in Latina women. The frequency of common variants was similar for cases and controls, but the frequency of common variants for African-American women significantly differed from those previously described for Caucasian women. We believe this to be the largest study of high-risk African-American and Latina women sequenced for variants in the BRCA1 gene to date.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue MS 44, Los Angeles, CA 90089-9175, USA. mckeanco@usc.edu
authors.forename: Roberta
authors.initials: R
authors.lastname: McKean-Cowdin
authors.forename: Heather
authors.initials: H
authors.lastname: Spencer Feigelson
authors.forename: Lucy Y
authors.initials: LY
authors.lastname: Xia
authors.forename: Celeste Leigh
authors.initials: CL
authors.lastname: Pearce
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D015331:Cohort Studies; D005192:Family Health / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D014644:Genetic Variation; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA
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