A polymorphism in theCYP17 gene is associated with prostate cancer risk

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Abstract
CYP17 encodes the enzyme cytochrome P‐450c17α, which mediates both 17α‐hydroxylase and 17,20‐lyase in the steroid biosynthesis pathway. A polymorphism 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 conducted a case‐control study of 63 patients with untreated histologically proven prostate cancer and 126 age‐matched control men with benign prostatic hyperplasia (BPH) to determine whether a polymorphism in the CYP17 gene is associated with prostate cancer risk. This polymorphism was investigated by PCR/RFLP using DNA from lymphocytes. The transition (T→C) in the risk allele (A2) creates a new recognition site for the restriction enzyme MspAI, which 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 the cancer group (23.8%) than in the BPH control group (9.5%). We found an increased 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 marked 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 size is rather small and the controls are BPH patients, our results suggest that the CYP17A2/A2 genotype may be a biomarker for prostate cancer risk, especially for older men. Int. J. Cancer 87:434–437, 2000.

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