Statin Use and Risk of Prostate Cancer: Results from a Population-based Epidemiologic Study

Ilir Agalliu; Claudia A. Salinas; Philip D. Hansten; Elaine A. Ostrander; Janet L. Stanford

Disclosures

Am J Epidemiol. 2008;168(3):250-260. 

In This Article

Abstract and Introduction

Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002-2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use. Logistic regression was used to generate odds ratios for ever use, current use, and duration of use. No overall association was found between statin use and prostate cancer risk (odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2 for current use; OR = 1.1, 95% CI: 0.7, 1.8 for >10 years' use), even for cases with more advanced disease. Risk related to statin use, however, was modified by body mass index (interaction p = 0.04). Obese men (BMI 30 kg/m2) who used statins had an increased risk (OR = 1.5, 95% CI: 1.0, 2.2) relative to obese nonusers, with a stronger association for longer-term use (OR = 1.8, 95% CI: 1.1, 3.0 for 5 years' use). Although statin use was not associated with overall prostate cancer risk, the finding of an increased risk associated with statin use among obese men, particularly use for extended durations, warrants further investigation.

Statin drugs are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the enzyme that controls conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, an essential precursor of cholesterol.[1,2,3] Statins are used to treat hypercholesterolemia and have been shown to reduce cardiovascular disease incidence and mortality.[4,5,6,7] Thus, use of statins has increased exponentially in the United States over the last decade.[8]

Statin use in relation to prostate cancer etiology is of interest because 1) these drugs inhibit the synthesis of cholesterol, a precursor of androgens that also plays a role in cell signaling pathways;[9] 2) mevalonate is necessary for the prenylation of proteins involved in signal transduction cascades downstream of membrane receptors that are crucial in cell growth and apoptosis;[10,11] and[3]) in experimental models, statins inhibit cell proliferation, inflammation, oxidative stress, angiogenesis, and metastasis.[2,3,11,12]

Some studies suggest that statins may alter prostate cancer risk. Randomized clinical trials of statin use to prevent cardiovascular disease reported no associations with prostate cancer incidence,[13,14,15] but such trials were limited by the short durations of use and brief follow-up periods.[16,17] Several observational studies showed an inverse association between statin use and risk of prostate cancer,[18,19,20,21,22,23] although others found no association.[24,25,26,27] The inverse association observed in some studies was limited to subgroups of men with advanced-stage disease;[20,23] current, more-than-5-year users with advanced disease;[21] or regular users of nonsteroidal antiinflammatory drugs.[22] An increase in overall prostate cancer risk was observed for statin users in two studies.[23,28] To further examine the potential relation between these widely used medications and risk of prostate cancer, we conducted a population-based case-control study.

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