Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation

Nat Genet. 1995 Dec;11(4):428-33. doi: 10.1038/ng1295-428.


Mutations in the BRCA1 gene, discovered in 1994, are associated with an 80-90% lifetime risk of breast cancer. We have analysed 60 families with a history of breast and/or ovarian cancer for germline mutations in BRCA1. Twenty-two different mutations were detected in 32 families (53%), of which 14 are previously unreported. We observed a significant correlation between the location of the mutation in the gene and the ratio of breast to ovarian cancer incidence within each family. Our data suggest a transition in risk such that mutations in the 3' third of the gene are associated with a lower proportion of ovarian cancer. Haplotype analysis supports previous data which suggest some BRCA1 mutation carriers have common ancestors; however, we have found at least two examples where recurrent mutations appear to have arisen independently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein
  • Breast Neoplasms / genetics*
  • Breast Neoplasms, Male / genetics
  • Female
  • Genetic Markers
  • Genetic Testing
  • Genotype
  • Germ-Line Mutation*
  • Haplotypes
  • Humans
  • Male
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics*
  • Phenotype
  • Risk Factors
  • Transcription Factors / genetics*


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