Shorter CAG repeat length in the androgen receptor gene is associated withmore aggressive forms of breast cancer

The androgen receptor (AR) is a transcription factor mediating the action o f androgens. The AR gene is localized on chromosome X and it contains a ser ies of CAG trinucleotide repeats. The length of the CAG repeats varies amon g individuals and this polymorphism is believed to be related to AR transcr iptional activity. Studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer . Although AR is expressed in breast cancer and the impact of androgen and AR on breast cancer has been recognized, the role of the CAG repeats in bre ast cancer remains unknown. In this study, we measured the CAG repeats in b reast cancer tissue using a PCR-based method. Of the 133 patients with prim ary breast cancer, 102 were heterozygous and 31 were homozygous. The mean C AG repeat number for homozygous women was 21; for heterozygous women the re peat number mean was 20 for the short allele and 24 for the long allele. Th e length of CAG repeats either in one allele or in both alleles was inverse ly correlated with the histological grade of breast cancer (r = -0.23 or -0 .26, respectively, p < 0.05). An association between positive lymph nodes a nd fewer CAG repeats in both alleles was also suggested (p = 0.06). Further more, survival analysis indicated that the total number of CAG repeats in b oth alleles was associated with patient overall survival. With every CAG re peat increase, there was a 6% reduction in the risk of death (RR = 0.94, p = 0.03). The association remained significant after controlling for the hom ozygous and heterozygous status (RR = 0.92, p = 0.01). The association beca me no longer significant when clinical and pathological variables were adju sted in the analysis but this could be due to the reduction of sample size in the multivariate analysis. CAG heterozygosity and difference in number o f CAG repeats between the two alleles were not associated with either disea se features or patient survival. Our results suggest that longer CAG repeat s may occur more frequently in less aggressive cancer and that the CAG repe ats may play a role in breast cancer progression.