Statins and Prostate Cancer Risk: A Case-Control Study

Abstract

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

HMG-CoA reductase inhibitors as adjuvant treatment for hematologic malignancies: what is the current evidence?

“…Of note, safety of this class of agents was confirmed by several meta-analyses [14,15]. Notwithstanding, several epidemiological studies have suggested that HMG-CoA reductase inhibitors may, in fact, prevent certain solid malignancies such as melanoma, breast, colon, and prostate cancers [16][17][18][19][20]. Likewise, it has been suggested that chronic statin use is linked with a trend toward a lower cancerrelated mortality rate [21].…”

Do Statins Affect Thyroid Volume and Nodule Size in Patients with Hyperlipidemia in a Region with Mild-to-Moderate Iodine Deficiency? A Prospective Study

“…However, Cappelli et al [16], in a retrospective study on 137 patients on statins (104 on simvastatin [hydrophobic], 29 on atorvastatin [hydrophilic], 1 on pravastatin, and 1 on rosuvastatin), did not detect a relationship between the number and volume of thyroid nodules and molecule type. While the duration of statin use is reportedly a stronger predictor than the daily dose for a reduction in the risk of developing prostate cancer, Shannon et al [37] concluded that nodules are less prevalent among patients taking a greater mean daily dose, independent of duration.…”

Hypercholesterolemia and prostate cancer: a hospital-based case–control study

“…Despite the different characteristics of the four study settings, an inverse association between longer-term use of statins and prostate cancer was observed in each, with point estimates of 0.26 [19], 0.60 [16], 0.57 [17] and 0.75 [18]. A small case-control study [20] of 100 men with prostate cancer recruited upon referral for biopsy found a 62% reduction in the risk of prostate cancer (OR = 0.38 [0.21-0.69]) with statin use. Lastly, a large population-based study reported by Teemu et al [21] showed no evidence for reduced overall prostate cancer risk among users of cholesterol-lowering drugs, but found a decreased risk of advanced cancer among statin users ( …”