Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2

Am J Hum Genet. 1996 Sep;59(3):547-53.


The common hereditary forms of breast cancer have been largely attributed to the inheritance of mutations in the BRCA1 or BRCA2 genes. However, it is not yet clear what proportion of hereditary breast cancer is explained by BRCA1 and BRCA2 or by some other unidentified susceptibility gene(s). We describe the proportion of hereditary breast cancer explained by BRCA1 or BRCA2 in a sample of North American hereditary breast cancers and assess the evidence for additional susceptibility genes that may confer hereditary breast or ovarian cancer risk. Twenty-three families were identified through two high-risk breast cancer research programs. Genetic analysis was undertaken to establish linkage between the breast or ovarian cancer cases and markers on chromosomes 17q (BRCA1) and 13q (BRCA2). Mutation analysis in the BRCA1 and BRCA2 genes was also undertaken in all families. The pattern of hereditary cancer in 14 (61%) of the 23 families studied was attributed to BRCA1 by a combination of linkage and mutation analyses. No families were attributed to BRCA2. Five families (22%) provided evidence against linkage to both BRCA1 and BRCA2. No BRCA1 or BRCA2 mutations were detected in these five families. The BRCA1 or BRCA2 status of four families (17%) could not be determined. BRCA1 and BRCA2 probably explain the majority of hereditary breast cancer that exists in the North American population. However, one or more additional genes may yet be found that explain some proportion of hereditary breast cancer.

Publication types

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

MeSH terms

  • Adult
  • BRCA1 Protein
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Female
  • Genetic Heterogeneity*
  • Genetic Linkage / genetics*
  • Genetic Markers
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Proteins / genetics*
  • North America
  • Ovarian Neoplasms / genetics
  • Pedigree
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • BRCA2 Protein
  • Genetic Markers
  • Neoplasm Proteins
  • Transcription Factors