Because androgens likely play a key role in prostate growth and prostate cancer development, variants of genes involved in androgen biosynthesis may be related to prostate cancer risk. The enzyme P450c17alpha, encoded by the CYP17 gene, catalyzes the conversion of progesterone and pregnenolone into precursors of potent androgens. In the 5' promoter region of the CYP17 gene, a T (A1 allele) to C substitution (A2 allele) has been hypothesized to increase CYP17 gene expression, resulting in higher levels of androgens. To investigate a possible role of CYP17 in prostate diseases, we evaluated the risk of prostate cancer and benign prostatic hyperplasia (BPH) in relation to variation in CYP17 genotype in a population-based case-control study conducted in Shanghai, China. The study included 174 prostate cancer cases, 182 BPH cases and 274 population controls. We observed no statistically significant overall associations of CYP17 genotypes with prostate cancer risk, although associations of the A1/A1 (odds ratio (OR) =1.42, 95% confidence interval (CI) 0.83-2.48) and A1/A2 (OR 1.41, 95% CI 0.91-2.17) genotypes with prostate cancer were suggested. A similar association of the A1/A1 genotype with BPH was suggested. We found no associations of CYP17 genotypes with serum sex hormone levels or other biomarkers after correction for multiple comparisons. Large population-based studies are needed to clarify whether CYP17 plays a role in prostate cancer risk and whether genotype effects vary in different racial/ethnic and other subgroups.
Copyright 2003 Wiley-Liss, Inc.