Steroid hormones, especially testosterone, play important roles in the carcinogenesis of prostate cancer, and several studies have reported changes in risk with polymorphisms of genes involved in steroid metabolism. One example is the CYP17 gene, which has a polymorphic T-to-C substitution in the 5'-untranslated region giving rise to A1 (T) and A2 (C) alleles. Steroid 5alpha-reductase type II (SRD5A2), which converts testosterone to the metabolically more active dihydrotestosterone, exhibits 2 polymorphisms: V89L, which substitutes leucine for valine at codon 89, and A49T, which substitutes threonine for alanine at codon 49. We therefore designed a case-control study of 105 prostate-cancer patients and 210 controls with benign prostatic hyperplasia for the purpose of investigating the association between prostate-cancer risk and polymorphisms in the SRD5A2 and CYP17 genes among the Japanese. The frequency of the CYP17 A2/A2 genotype in cases (18.8%) was higher than in controls (14.5%). Compared with the A1/A1 genotype, the odds ratio for the A2/A2 genotype was 2.39 (95% confidence interval 1.04-5.46, p = 0.04). The frequency of the SRD5A2 LL genotype in cases (29.3%) was also slightly higher than in controls (24.6%), but this was not significant. Regarding the A49T polymorphism of SRD5A2, we could not detect the T allele in any of the examined samples. These data suggest a significant association between the CYP17 polymorphism and prostate-cancer risk among the Japanese. Copyright 2001 Wiley-Liss, Inc.