Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families

Nat Genet. 1994 Dec;8(4):392-8. doi: 10.1038/ng1294-392.

Abstract

Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22-23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • BRCA1 Protein
  • Base Sequence
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Canada / epidemiology
  • DNA Primers
  • Female
  • Frameshift Mutation*
  • Haplotypes
  • Humans
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Transcription Factors / genetics*

Substances

  • BRCA1 Protein
  • DNA Primers
  • Neoplasm Proteins
  • Transcription Factors