Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer

N Engl J Med. 1996 Jan 18;334(3):143-9. doi: 10.1056/NEJM199601183340302.


Background: Mutations in a germ-line allele of the BRCA1 gene contribute to the familial breast cancer syndrome. However, the prevalence of these mutations is unknown in women with breast cancer who do not have the features of this familial syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, because early onset is characteristic of a genetic predisposition to cancer.

Methods: Clinical information and peripheral-blood mononuclear cells were obtained from 418 women from the Boston metropolitan area in whom breast cancer was diagnosed at or before the age of 40. A comprehensive BRCA1 mutational analysis, involving automated nucleotide sequencing and a protein-truncation assay, was undertaken in 30 of these women, who had breast cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish population, was sought with an allele-specific polymerase-chain-reaction assay in 39 Jewish women among the 418 women who had breast cancer at or before the age of 40.

Results: Among 30 women with breast cancer before the age of 30, 4 (13 percent) had definite, chain-terminating mutations and 1 had a missense mutation. Two of the four Jewish women in this cohort had the 185delAG mutation. Among the 39 Jewish women with breast cancer at or before the age of 40, 8 (21 percent) carried the 185delAG mutation (95 percent confidence interval, 9 to 36 percent).

Conclusions: Germ-line BRCA1 mutations can be present in young women with breast cancer who do not belong to families with multiple affected members. The specific BRCA1 mutation known as 185delAG is strongly associated with the onset of breast cancer in Jewish women before the age of 40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / ethnology*
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Germ-Line Mutation*
  • Humans
  • Jews*
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Prevalence
  • Retrospective Studies
  • Transcription Factors / genetics*


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