BRCA1 mutations in a population-based sample of young women with breast cancer

N Engl J Med. 1996 Jan 18;334(3):137-42. doi: 10.1056/NEJM199601183340301.


Background: Inherited mutations in the BRCA1 gene are associated with a high risk of breast and ovarian cancer in some families. However, little is known about the contribution of BRCA1 mutations to breast cancer in the general population. We analyzed DNA samples from women enrolled in a population-based study of early-onset breast cancer to assess the spectrum and frequency of germ-line BRCA1 mutations in young women with breast cancer.

Methods: We studied 80 women in whom breast cancer was diagnosed before the age of 35, and who were not selected on the basis of family history. Genomic DNA was studied for BRCA1 mutations by analysis involving single-strand conformation polymorphisms and with allele-specific assays. Alterations were defined by DNA sequencing.

Results: Germ-line BRCA1 mutations were identified in 6 of the 80 women. Four additional rare sequence variants of unknown functional importance were also identified. Two of the mutations and three of the rare sequence variants were found among the 39 women who reported no family history of breast or ovarian cancer. None of the mutations and only one of the rare variants was identified in a reference population of 73 unrelated subjects.

Conclusions: Alterations in BRCA1 were identified in approximately 10 percent of this cohort of young women with breast cancer. The risk of harboring a mutation was not limited to women with family histories of breast or ovarian cancer. These results represent a minimal estimate of the frequency of BRCA1 mutations in this population. Comprehensive methods of identifying BRCA1 mutations and understanding their importance will be needed before testing of women in the general population can be undertaken.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Germ-Line Mutation*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • Genetic Markers
  • Neoplasm Proteins
  • Transcription Factors