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.

A recent study from deCode reported an association between common variants in the region 8q24 and prostate cancer risk. The strongest association was found with the single nucleotide polymorphism rs1447295. We genotyped 821 prostate cancer cases and 732 population controls for rs1447295 to test the association between this common variant and prostate cancer risk, and examine whether this association depends on Gleason score. Our case-control study confirmed the association between rs1447295 and prostate cancer risk (P = 0.0005). The odds ratio (OR) for prostate cancer was 1.52 [95% confidence interval (CI), 1.20-1.93] for carriers of any A allele compared with noncarriers. The OR for Gleason score 5 to 6 prostate cancer (1.48; 95% CI, 1.13-1.95) was similar to the OR for Gleason score 7 to 10 prostate cancer (1.58; 95% CI, 1.18-2.11, P for heterogeneity = 0.7). We conclude that the A allele of rs1447295 is associated with a higher risk of prostate cancer regardless of tumor aggressiveness, suggesting that such a variant, or a variant in linkage disequilibrium with it, plays a role early in prostate carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2007;16(3):610 -2)

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