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June 21, 2006

Statins and the Risk of Cancer—Reply

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2006;295(23):2720-2722. doi:10.1001/jama.295.23.2721-b

In Reply: Dr Duncan and colleagues raise questions about the categorization of hydrophilicity and lipophilicity in the subgroup analysis. There are 3 levels of lipophilicity for statins. Pravastatin and rosuvastatin have low lipophilicity, atorvastatin and fluvastatin have modest lipophilicity, and simvastatin and lovastatin have high lipophilicity.1 Pravastatin, fluvastatin, and atorvastatin do not penetrate the blood-brain barrier.2 From postmarketing surveillance, the risk of death from rhabdomyolysis is quite similar between pravastatin, fluvastatin, and atorvastatin, but lower than that of simvastatin and lovastatin.3 We therefore believe that fluvastatin and atorvastatin act more like hydrophilic agents than lipophilic ones. However, when we analyzed pravastatin alone for breast cancer incidence, the results (odds ratio [OR], 1.38; 95% confidence interval [CI], 0.72-2.65) were similar to our overall statin findings, as they were for colon, gastrointestinal, and respiratory cancer incidence. Pravastatin therefore does not appear to exhibit procancer effects that might have countered the anticancer effects of other statins included in our analysis.