Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2)

Prostate cancer is the most common malignancy in males and is the second mo st common cause of cancer mortality in American men, Polymorphisms have bee n identified in two genes, the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5-reductase type II gene (SRD5A2) that are involved with an drogen biosynthesis and metabolism. The CYP17 A2 allele contains a T-->C tr ansition in the 5' promoter region that creates an additional Spl-type (CCA CC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels. We tested genotyp es in 108 prostate cases and 167 controls along with samples (n = 340) from several different ethnic groups. The CYP17 A2 allele (combined A1/A2 and A 2/A2 genotypes) occurred at a higher frequency in Caucasian patients with p rostate cancer (70%) than in Caucasian clinical control urology patients (5 7%), suggesting that the A2 allele may convey increased risk for prostate c ancer [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.0-3.0]. Blac ks and Caucasians had a similar frequency of the A2 genotype (16 and 17%, r espectively) while Taiwanese had the highest frequency (27%), The SRD5A2 le ucine genotype was most frequent in Taiwanese (28%), intermediate in Caucas ians (8.5%) and lowest in Blacks (2.5%), Genotypes having a SRD5A2 leucine allele were somewhat more common in prostate cancer cases (56%) than in con trols (49%) (OR = 1.4, 95% CI = 0.8-2.2) but this difference was not signif icant. These results support the hypothesis that some allelic variants of g enes involved in androgen biosynthesis and metabolism may be associated wit h prostate cancer risk.