A polymorphism in the CYP17 gene is associated with prostate cancer risk

CYP17 encodes the enzyme cytochrome P-450c17 alpha, which mediates both 17 alpha-hydroxylase and 17,20-lyase in the steroid biosynthesis pathway. A po lymorphism in the 5' promoter region of the CYP17 gene has been described. Steroid hormones, especially androgens, are believed to play a key role in the etiology of prostate cancer, Therefore, polymorphisms in genes involved in the androgen metabolism may affect the risk of prostate cancer. We cond ucted a case-control study of 63 patients with untreated histologically pro ven prostate cancer and 126 age-matched control men with benign prostatic h yperplasia (BPH) to determine whether a polymorphism in the CYP17 gene is a ssociated with prostate cancer risk. This polymorphism was investigated by PCR/RFLP using DNA from lymphocytes. The transition (T-->C) in the risk all ele (A2) creates a new recognition site for the restriction enzyme MspA1, w hich permits designation of the wildtype (A1) and the risk allele (A2), The prevalence of the A2/A2 genotype was significantly higher (P = 0.03) in th e cancer group (23.8%) than in the BPH control group (9.5%). We found an in creased risk in men carrying 2 A2 alleles (OR = 2.80, 95% CI = 1.02-77.76). For carrier with at least 1 A2 allele, the OR was 0.90 (95% CI = 0.43-1.89 ). After stratification by median age (66 years) at time of diagnosis, a ma rked increased risk was found in carriers of the A2/A2 genotype older than 66 years (OR = 8.93, 95% CI = 1.78-49.19, P = 0.01). Although the sample si ze is rather small and the controls are BPH patients, our results suggest t hat the CYP17A2/A2 genotype may be a biomarker for prostate cancer risk, es pecially for older men. Int. J, Cancer 87:434-437, 2000. (C) 2000 Wiley-Lis s, Inc.