Original Articles5α-Reductase 2 polymorphisms as risk factors in prostate cancerSöderström, Torbjörna; Wadelius, Miaa; Andersson, Swen-Olovb; Johansson, Jan-Erikb; Johansson, Sarac; Granath, Fredrikd; Rane, AnderseAuthor Information aDepartment of Medical Sciences, Clinical Pharmacology, University Hospital, S-751 85 Uppsala, Sweden, bDepartment of Urology, Örebro Medical Centre, S-701 85 Örebro, Sweden, cDepartment of Medical Sciences, Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden, dDepartment of Medical Epidemiology, Karolinska Institutet, SE-171 77 Stockholm, Sweden and eDepartment of Medical Laboratory Sciences and Technology, Karolinska Institutet, Division of Clinical Pharmacology, Huddinge University Hospital, SE-141 86 Stockholm, Sweden Correspondence to Torbjörn Söderström, Medical Sciences, Clinical Pharmacology, University Hospital, SE-751 85 Uppsala., Sweden Tel.: +46 18 61113887; fax: +46 18 51 92 37; e-mail: [email protected] Received 21 September 2001 Accepted 9 January 2002 Pharmacogenetics: June 2002 - Volume 12 - Issue 4 - p 307-312 Buy Abstract Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5α-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/ Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/ Km ratio. We performed a population-based case–control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44–22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases. © 2002 Lippincott Williams & Wilkins, Inc.