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To the Editor: In their meta-analysis, Dr Dale and colleagues¹ stratified cancer risk associated with statin use according to the hydrophilicity or lipophilicity of the individual drugs. This physicochemical property affects uptake of a particular statin by extrahepatic cells, including malignant cells, in which it can inhibit cell growth by down-regulating the synthesis of mevalonate.² In interpreting this study, there are 2 points that should be addressed.

First, although atorvastatin and fluvastatin were classified (along with pravastatin) as hydrophilic statins, they are usually considered to be lipophilic.³ Unlike hydrophilic pravastatin, atorvastatin and fluvastatin readily enter extrahepatic cells,³ including cancer cells.⁴ No rationale was given for the classification of these statins as hydrophilic.

Second, site-specific cancer risk should be analyzed separately for hydrophilic pravastatin and the lipophilic statins, because it is biologically plausible that pravastatin may increase the risk of some extrahepatic cancers.² Serum cholesterol lowering causes a compensatory induction of . . . [Full Text of this Article]

Robin E. Duncan, PhD
robin_duncan@berkeley.edu
Departments of Nutritional Sciences and Toxicology
University of California
Berkeley

Ahmed El-Sohemy, PhD; Michael C. Archer, PhD, DSc
Department of Nutritional Sciences
University of Toronto
Toronto, Ontario

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