Androgen receptor CAG repeat length in Jewish Israeli women who are BRCA1/2 mutation carriers: association with breast/ovarian cancer phenotype

Eur J Hum Genet. 2002 Nov;10(11):724-8. doi: 10.1038/sj.ejhg.5200880.

Abstract

BRCA1/2 mutation carriers are at an increased risk for developing breast and/or ovarian cancer. Yet, the genetic and environmental factors that govern the phenotypic expression of mutant BRCA1/2 alleles remain elusive. The CAG repeat within exon 1 of the androgen receptor (AR) gene is reportedly associated with breast cancer phenotype in BRCA1 mutation carriers. Two hundred and twenty seven BRCA1/2 mutation carriers were genotyped for the polymorphic AR CAG repeat, and allele size was correlated with breast/ovarian cancer morbidity parameters. Of 227 BRCA1/2 carriers, 169 were BRCA1 mutation carriers and 58 carried a BRCA2 mutation, 149 had breast and/or ovarian cancer and 78 were asymptomatic mutation carriers. The mean age at diagnosis in women with either or both neoplasms was 46.7+/-11.2 years, and that of the asymptomatic group - 45.8+/-9.4 years, a statistically insignificant difference. The AR CAG repeat ranged from eight to 28 in all tested women, and the mean number of the repeats were not statistically different between affected (18.3+/-2.4) and asymptomatic mutation carriers (18.6+/-2.1). The AR CAG repeat among patients with early onset (<42 years) breast cancer was significantly shorter (17.5+/-2.3) compared with asymptomatic individuals (18.6+/-2.1) (P<0.01), and the shorter allele - the younger the age at diagnosis. There is no conclusive evidence of association between AR CAG repeat size and breast or ovarian cancer risk in Jewish BRCA1/2 mutation carriers. A small effect of a short AR CAG allele size on breast cancer at early age (<42 years) cannot be excluded.

MeSH terms

  • Adult
  • Breast Neoplasms / genetics
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genotype
  • Humans
  • Israel
  • Middle Aged
  • Ovarian Neoplasms / genetics
  • Phenotype
  • Receptors, Androgen / genetics*
  • Trinucleotide Repeats*

Substances

  • Receptors, Androgen