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

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.