Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases

Cancer. 2000 Mar 15;88(6):1393-402. doi: 10.1002/(sici)1097-0142(20000315)88:6<1393::aid-cncr17>;2-p.


Background: There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population-based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes.

Methods: Subjects were drawn from two population-based, case-control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first-degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features.

Results: Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first-degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma.

Conclusions: Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Carcinoma / genetics*
  • Case-Control Studies
  • Codon / genetics
  • Confidence Intervals
  • Female
  • Frameshift Mutation / genetics
  • Genes, BRCA1 / genetics*
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics*
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation, Missense / genetics
  • Neoplasm Proteins / genetics*
  • Ovarian Neoplasms / genetics
  • Polymorphism, Genetic / genetics
  • Population Surveillance
  • Risk Factors
  • Transcription Factors / genetics*


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