An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium

Am J Hum Genet. 1995 Jan;56(1):254-64.


The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of the 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer-family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.

MeSH terms

  • Adult
  • Age of Onset
  • BRCA1 Protein
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms, Male / epidemiology
  • Breast Neoplasms, Male / genetics
  • Chromosomes, Human, Pair 17*
  • Female
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease
  • Humans
  • Iceland / epidemiology
  • Lod Score
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasms, Multiple Primary / epidemiology
  • Neoplasms, Multiple Primary / genetics
  • Neoplastic Syndromes, Hereditary / epidemiology
  • Neoplastic Syndromes, Hereditary / genetics*
  • Netherlands / epidemiology
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Transcription Factors / genetics*


  • BRCA1 Protein
  • Neoplasm Proteins
  • Transcription Factors