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 mevalonate synthesis in extrahepatic cells, and we have shown that in mice mevalonate promotes the growth of tumors derived from human breast cancer cells.5 Although lipophilic statins can readily penetrate biological membranes to mitigate this compensatory induction through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, hydrophilic pravastatin cannot.
Pooling of cancer site data for all types of statins may temper findings of risk where one exists. The study by Dale et al found no significant effect of statin use on cancer risk at any particular site but did report significant heterogeneity among the studies for breast cancer risk. This heterogeneity may be because increased breast cancer risk occurs only in users of pravastatin, but not in users of lipophilic statins.2
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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