Observational studies have shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use may be associated with reduced cancer risk. The purpose of this case-control study was to elucidate the association between statin use and prostate cancer risk. Prostate cancer cases (n ¼ 100), recruited upon referral for prostate biopsy, and frequency age-matched, prostate-specific antigen-normal clinic controls (n ¼ 202) were recruited from the Portland, Oregon, Veterans Affairs Medical Center. Information on any use of statins from May 1997 through August 2004 was obtained from an electronic pharmacy database. Days of use, type of statin, dose, and prescription changes were recorded. Duration and intensity were calculated for each statin type on the basis of days of use and prescribed dose. Thirty-six percent of cases and 49 percent of controls had a record of any statin use. Following adjustment for other potential risk factors, statin use was associated with a significant reduction in prostate cancer risk (odds ratio ¼ 0.38, 95% confidence interval: 0.21, 0.69). Furthermore, in analyses stratified by Gleason score, the inverse association with statin use was maintained only among men with Gleason scores of 7 (odds ratio ¼ 0.24, 95% confidence interval: 0.11, 0.53). The results of this case-control study suggest that statins may reduce the risk of total prostate cancer and, specifically, more aggressive prostate cancer.case-control studies; cholesterol; hydroxymethylglutaryl-CoA reductase inhibitors; mevalonic acid; prostatespecific antigen; prostatic neoplasms; veterans Abbreviations: CI, confidence interval; FPP, farnesylpyrophosphate; GGPP, geranylgeranyl pyrophosphate; NSAID, nonsteroidal antiinflammatory drug; OR, odds ratio; p21, M r 21,000 protein (p27 defined similarly); PVAMC, Portland Veterans Affairs Medical Center; VA, Veterans Affairs.One in six men over age 60 years will be diagnosed with prostate cancer (1). Prostate cancer is the second leading cause of cancer deaths among US men (2). Therefore, the need to identify and to develop means to prevent this common malignancy is a high priority. Recent research on the chemopreventive potential of a group of cholesterollowering drugs, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), has shown intriguing results (3, 4). Statins lower serum cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-determining enzyme in the mevalonate pathway (4). In addition to their cholesterol-lowering ability, statins have been shown to inhibit prostate and breast cancer cell proliferation and to induce tumor-specific apoptosis (4-6) in in vitro studies.While the mechanism remains unclear, clinical trials with cancer as a secondary endpoint have shown a nonsignificant inverse association between statin use and total cancer incidence (7,8). Additionally, Bjerre and LeLorier's metaanalysis (9) of five trials of statins and cardiovascular

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