BRCA1 and BRCA2 founder mutations in patients with bilateral breast cancer

Eur J Hum Genet. 1999 Oct-Nov;7(7):833-6. doi: 10.1038/sj.ejhg.5200371.


Bilateral breast cancer is traditionally considered an indirect indicator of inherited predisposition to cancer. To appreciate the contribution of genetic determinants to bilateral breast cancer in Jewish women we genotyped 55 such women for the three predominant mutations in BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) that account for the overwhelming majority of BRCA mutations in high-risk Jewish families. Among women with bilateral breast cancer, 17 mutation carriers (17/55; 29.6%) were identified. Individual mutation frequencies were 18.5% (10/55) for 185delAG, 3.7% (2/55) for 5382insC and 7.4% (5/55) for 6174delT. Carrier rate was significantly higher (P < 0.0016) in women with bilateral breast cancer whose first tumour was diagnosed at or before 42 years of age (82%; 14/17) than in women diagnosed after 42 years of age (7.9%; 3/38). Among patients with bilateral breast cancer and positive family history 45% (14/31) carried a BRCA mutation. Of these 86% (12/14) had one breast cancer diagnosed at or before 42 years of age. Our results suggest that bilateral breast cancer per se, in most cases, does not reflect genetic predisposition, unless associated with early age of onset (first tumour diagnosed at or before 42 years of age). Although the relationship between young age and carrier state in women with bilateral breast cancer is strong, no significant association between family history and carrier state was found. We can thus speculate that women with early onset breast cancer who carry a BRCA1 or BRCA2 mutation are prone to acquire a second breast tumour.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Female
  • Founder Effect*
  • Genes, BRCA1 / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Jews / genetics
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Transcription Factors / genetics*


  • BRCA2 Protein
  • Neoplasm Proteins
  • Transcription Factors