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

✍ Scribed by Andrea Gsur; Gabriele Bernhofer; Sonja Hinteregger; Gerald Haidinger; Georg Schatzl; Stephan Madersbacher; Michael Marberger; Christian Vutuc; Michael Micksche

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 63 KB
• Volume: 87
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/1097-0215(20000801)87:3<434::aid-ijc19>3.0.co;2-g

✦ Synopsis

CYP17 encodes the enzyme cytochrome P-450c17␣, which mediates both 17␣-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 (T3 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.