BRCA1 variants in a family study of African-American and Latina women

Hum Genet. 2005 May;116(6):497-506. doi: 10.1007/s00439-004-1240-5. Epub 2005 Feb 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • African Americans / genetics*
  • Aged
  • Breast Neoplasms / genetics*
  • Chromosome Mapping
  • Cohort Studies
  • Family Health / ethnology
  • Female
  • Gene Frequency
  • Genes, BRCA1*
  • Genetic Variation
  • Hispanic Americans / genetics*
  • Humans
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Sequence Analysis, DNA