Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility

The length of a polymorphic CAG repeat in exon 1 of the androgen receptor (AR) is inversely correlated with AR transactivation activity. As heightened androgenic stimulation may oppose breast cell proliferation, which is mediated by AR, we examined whether AR-CAG repeat lengths are related to breast cancer susceptibility. A nested case-control study of 88 newly diagnosed cases of breast cancer between 1992 and 2000 and 334 matched controls was carried out in Taiwanese women. Risk factors were obtained through a standardized questionnaire interview and blood samples were collected and used to determine the number of AR-CAG repeats. Women with one or more long AR (CAG)n repeat alleles (>22 repeats) were not at significantly increased risk of breast cancer [odds ratio (OR), 1.52; 95% confidence interval (CI), 0.80-2.90]. Of particular interest was a significantly increased risk associated with the long-allele AR genotype that was present mostly among women with a short duration (<10 years) of early estrogen exposure, as indicated by the interval between age at menarche and age at first full-term pregnancy, as compared with short AR allele genotypes (OR, 2.70; 95% CI, 1.00-7.31), although no such significant association in women with a long duration of early estrogen exposure (OR, 0.70; 95% CI, 0.25-1.59) was detected. These data suggest that longer AR (CAG)n repeat alleles may confer an increased risk of breast cancer among particular subsets of individuals, although these findings need replication in other populations.