The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women

Am J Hum Genet. 1997 Mar;60(3):505-14.


The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Female
  • Founder Effect
  • Haplotypes
  • Heterozygote
  • Humans
  • Iraq
  • Jews / genetics*
  • Male
  • Middle Aged
  • Morbidity
  • Mutagenesis, Insertional
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Neoplasms, Second Primary / genetics
  • Ovarian Neoplasms / ethnology
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Risk Factors
  • Sequence Deletion
  • Transcription Factors / genetics*


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