Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial Teemu J. Murtola 1,2 , Teuvo L.J. Tammela 3,4 , Liisa Ma ¨a ¨tta ¨nen 5 , Heini Huhtala 1 , Elizabeth A. Platz 6 , Martti Ala-Opas 7 , Ulf-Ha ˚ kan Stenman 8 and Anssi Auvinen 1 1 Department of Epidemiology, University of Tampere, School of Public Health, Tampere, Finland 2 Central Finland Central Hospital, Jyva ¨skyla ¨, Finland 3 Department of Urology, Tampere University Hospital, Tampere, Finland 4 Medical School, University of Tampere, Tampere, Finland 5 The Finnish Cancer Registry, Helsinki, Finland 6 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 7 Department of Urology, Helsinki University Hospital, Helsinki, Finland 8 Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland Decreased risk of advanced prostate cancer has been reported among men using statins. However, the evidence on overall prostate cancer risk is conflicting. We compared the relative risk between current users and non-users of statins or other cholesterol-lowering medications in a population undergoing systematical prostate cancer screening. The study cohort comprised of 23,320 men participating in the screening arm of the Finnish prostate cancer screening trial during 1996–2004. Information on medication use was obtained from a comprehensive national prescription database. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HRs) for prostate cancer. Serum prostate-specific antigen (PSA) level was compared between current users and non-users of cholesterol-lowering drugs. Compared with medication non-users, the overall prostate cancer incidence was decreased among statin users [HR 0.75, 95% confidence interval (CI) 0.63–0.89]. The inverse association was dose-dependent with cumulative amount of statin use, and strongest for low-grade and early stage tumors. The incidence was nonsignificantly lower also among users of other types of cholesterol- lowering drugs (HR 0.62, 95% CI 0.28–1.38), but without dose-dependence. Age-adjusted median serum PSA tended to be lower among users of cholesterol-lowering drugs, but the relative risk decrease among statin users was not related to decreased PSA. Overall incidence of prostate cancer was lowered among statin users when bias due to differential PSA testing between medication users and non-users was eliminated by systematical prostate cancer screening. Cholesterol-lowering with statins seems beneficial for prostate cancer prevention. A group of cholesterol-lowering drugs, 3-hydroxy-3-methyl- glutaryl coenzyme A reductase inhibitors (statins) have shown prostate cancer growth inhibiting potential both in vitro and in animal studies. 1 Additionally, several epidemio- logical studies have consistently reported lower risk of advanced prostate cancer especially in long-term statin users, 1,2 suggesting that statins could prevent progression of prostate tumors into advanced stage. However, evidence on statins’ effect on overall prostate cancer risk has been more controversial, 1–7 some studies finding no effect or even increased overall prostate cancer risk, while other studies have reported reduced overall risk. Use of other groups of cholesterol-lowering drugs (fibric acid-derivatives or fibrates, bile acid-binding resins and nico- tinic acid with its derivatives) has not been associated with prostate cancer risk. 1 One likely explanation for the conflicting results regarding overall prostate cancer risk in statin users is the confounding effect of more active serum prostate-specific antigen (PSA) testing among medication users under medical surveillance. 8 PSA testing strongly influences the overall prostate cancer Key words: epidemiology, incidence, prostate cancer, prostate-specific antigen, statins Abbreviations: BMI: body mass index; CI: confidence interval; CVD: cardiovascular disease; DDD: defined daily dose; HR: hazard ratio; PSA: prostate-specific antigen; SII: Social Insurance Institution of Finland Grant sponsor: Academy of Finland; Grant number: 205 862; Grant sponsors: Competitive Research Funding of Tampere University Hospital, the Finnish Cancer Society, Hospital District of Central Finland, Pirkanmaa Regional Fund of the Finnish Cultural Foundation, Irja Karvonen cancer trust, The Finnish Cancer Organizations and nonrestricted grants from Astellas, Schering Foundation, research foundation of Orion Pharma, Pfizer and Abbott Pharma DOI: 10.1002/ijc.25165 History: Received 10 Aug 2009; Accepted 21 Dec 2009; Online 13 Jan 2010 Correspondence to: Teemu J. Murtola, University of Tampere, School of Public Health, Department of Epidemiology, Tampere, Finland, Tel.: þ358 40 5813177, Fax: þ358-14-269-1098, E-mail: teemu.murtola@uta.fi Epidemiology Int. J. Cancer: 127, 1650–1659 (2010) V C 2010 UICC International Journal of Cancer IJC