| The androgen receptor (AR) gene contains a CAG microsatellite polymorphism and the number of repeats may influence AR transactivation strength. Prostate-specific antigen (PSA) gene expression is tightly regulated by androgens via three androgen response elements (AREs). The PSA promoter contains two polymorphisms, a G/A transition at position −158 in ARE-I and a G/A transition at position −252. We conducted a case-control study nested within the Cardiovascular Health Study to test the hypothesis that PSA haplotype, defined by the alleles at positions −158 and −252 on the same chromosome, either alone or in conjunction with AR CAG length, was related to prostate cancer risk. No significant association was observed between PSA genotype and prostate cancer. A 1.5-fold (95% CI, 1.1–2.2) increased risk of prostate cancer was observed among men with <21 AR CAG repeats. Men who were homozygous for the PSA *2 (−252G/−158G) haplotype and possessed <21 AR CAG repeats had a 2.6-fold (95% CI, 0.9–7.2) increased risk of developing prostate cancer compared to men with no copies of PSA *2 and ≥21 AR CAG repeats. A significant 4.6-fold (95% CI, 1.4–15.8) increased risk of advanced disease was observed with the combination of short AR CAG alleles and the PSA *2*2 genotype. These data are suggestive of an interaction between the AR and PSA genes in mediating prostate cancer risk. |
