The E211 G>A Androgen Receptor Polymorphism Is Associated with a Decreased Risk of Metastatic Prostate Cancer and Androgenetic Alopecia

Abstract

The androgen receptor (AR) gene encodes a transcription factor, which mediates androgen action in target tissues, including the prostate. Prostate cancer is androgen dependent, implicating AR in susceptibility to this male condition. Male pattern balding, androgenetic alopecia, has recently been associated with prostate cancer, suggesting shared androgen pathways. The CAG and GGC repeats in the AR have been studied extensively as markers of prostate cancer susceptibility, with inconclusive findings, whereas the AR-E211 G>A polymorphism has been associated with androgenetic alopecia. We assessed the repeat linked single nucleotide polymorphism as a marker of risk association in prostate cancer, including androgenetic alopecia, in an Australian population-based case-control study. In 815 prostate cancer cases and 719 controls, the proportion of A-allele carriers was the same in each group. Overall, there was no evidence for an association between the A allele and risk of prostate cancer, however, the proportion of A-allele carriers in metastatic prostate cancer (5%) was lower than in less advanced disease (16%, P = 0.03). The proportion of A-allele carriers was 24% in nonbald men but it was lower in men with vertex alopecia alone (13%, P = 0.001) or in combination with frontal alopecia (7%, P < 0.0001). This inverse association between the A allele and baldness was independent of prostate cancer status (P for interaction = 0.2). These results suggest that the AR-E211 A allele, in linkage with the functional repeat sequences, is associated with a lower risk of metastatic prostate cancer and a lower risk of alopecia.