Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial

Abstract

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 cholesterollowering 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.

Long-term Use of Cholesterol-Lowering Drugs and Cancer Incidence in a Large United States Cohort

“…Our null results with respect to long-term use and risk of prostate, breast, and colorectal cancer are consistent with results from most previous studies of long-term use of statins. Of studies that included at least 20 cases of breast (11,(21)(22)(23)(24), prostate (11,18,(24)(25)(26)(27)(28), or colorectal cancer (11,(29)(30)(31)(32), with 4 or more years of use, only 2 (26, 29) reported a statistically significant reduction in risk.…”

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

“…The presence of antiandrogenic effects of statins and not of fibrates and acipimox and colestipol are supported by the findings in a Finnish epidemiological study. This study showed statins to have a beneficial effect on prostate cancer prevention; this effect was not found for fibrates, acipimox and colestipol [19]. The finding of docosahexaenoic acid as positive was unexpected, but another polyunsaturated fatty acid "γ-linolenic acid" was also found to be positive in a previous study [4].…”

“…• Possible AR antagonism according to the literature [11][12][13][14][15][16][17][18][19][20][21] • Part of a drug group • The presence of a biophore • The presence of an unknown fragment • Overall a distribution between positive and negative corresponding to about 25% and 75%, respectively; two times the presence of positives previously found for the EINECS chemicals [4,5]. 100 drugs were selected due to these criteria.…”

“…Secondary anti-androgenic effect is found for the diureticum spironolactone and probably also for the antiarrhytmics quinidine, procainamide, disopyramide, sotalol, amiodarone, ibutilide and dofitilide [4,7,8,[11][12][13][14][15]. Several epidemiological studies have related statins to improvement of prostate cancer treatment [16][17][18][19]. Statins are also related to improvement of treatment of acne and Polycystic ovary syndrome (PCOS) [20,21] -diseases that involve high testosterone levels.…”

Epithelial cell migration as a potential therapeutic target in early lung cancer

“…Similarly, treatment of human cultured prostate cancer cells with simvastatin or rosuvastatin reduced colony-forming ability and migration towards the powerful chemoattractant bone marrow stroma, with normal migratory behaviour restored with the addition of mevalonate or GGPP [43]. In addition, epidemiological data demonstrate lower rates of prostate cancer progression in patients taking statins [44][45][46].…”