Statins and Cancer

Abstract

To the Editor: In their recently published case–control trial, Coogan et al., reported that statin use was not associated with the risk of 10 cancers at extra-hepatic sites.1 Different statins are frequently grouped together as a drug class since they share a major biochemical function—inhibition of hepatic HMG-CoA reductase. However, there is considerable evidence that the hydrophobic and hydrophilic statins differ in their biochemical function at extra-hepatic sites.2 Grouping these compounds together for the purpose of analyzing a cancer risk in extra-hepatic tissues may mask an effect where one exists. Hydrophilic pravastatin does not enter most normal extra-hepatic cells or malignant cells of extra-hepatic origin. This precludes a protective effect of this statin on the growth of malignant cells at most extra-hepatic sites. Failure to distinguish cancer risk data between users of hydrophobic and hydrophilic statins, therefore, may temper findings of a protective effect where one exists. Furthermore, it is biologically plausible that hydrophilic statins such as pravastatin that lower serum cholesterol but do not enter most extra-hepatic cells may actually increase the risk of some extra-hepatic cancers. Lowering serum cholesterol causes a compensatory induction of HMG-CoA reductase in extra-hepatic cells. We have shown that mevalonate, the product of this enzyme, can promote the growth of tumors derived from human cells in mice.3 Although lipophilic statins can readily enter extra-hepatic cells to inhibit HMG-CoA reductase activity and compensate for the induction of this enzyme, hydrophilic statins cannot. Grouping of hydrophilic and hydrophobic statins in studies of their extra-hepatic effects without regard to fundamental differences in their extra-hepatic function may, therefore, obscure findings of risk where one exists. Robin E. Duncan Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA [email protected] Ahmed El-Sohemy Michael C. Archer Department of Nutritional Sciences, University of Toronto, Toronto, Ontario