title: A polymorphism in the CYP17 gene is associated with prostate cancer risk.
abstract: CYP17 encodes the enzyme cytochrome P-450c17 alpha, which mediates both 17 alpha-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.
authors.affiliation: Department of Applied and Experimental Oncology, Institute of Cancer Research, University of Vienna, Vienna, Austria. andrea.gsur@univie.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Gsur
authors.forename: G
authors.initials: G
authors.lastname: Bernhofer
authors.forename: S
authors.initials: S
authors.lastname: Hinteregger
authors.forename: G
authors.initials: G
authors.lastname: Haidinger
authors.forename: G
authors.initials: G
authors.lastname: Schatzl
authors.forename: S
authors.initials: S
authors.lastname: Madersbacher
authors.forename: M
authors.initials: M
authors.lastname: Marberger
authors.forename: C
authors.initials: C
authors.lastname: Vutuc
authors.forename: M
authors.initials: M
authors.lastname: Micksche
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D000483:Alleles; D000728:Androgens / Q000378:metabolism*; D015415:Biomarkers; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000502:physiology
chemical_list: D000728:Androgens; D015415:Biomarkers; D013254:Steroid 17-alpha-Hydroxylase