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Do Statins Cause Cancer?

Animal studies show that all statins as well as fibrates can cause benign and malignant tumors of various organs at exposure levels similar to those prescribed for humans. However, I am not aware of any proof that this is due to promoting angiogenesis by VEGF or other effects, although this has been suggested (Med Hypotheses 2002; 58:85-6.) and would appreciate references to support this from anyone. Statins do promote the proliferation of endothelial cells via the protein kinase B pathway (Rev Esp Cardiol 2002 Aug;55(8):838-44) and since this is independent of lipid lowering effects, it has been proposed that this may explain some of their benefits in coronary disease by encouraging vasculogenesis (Nat Med. 2000 Sep;6(9):965-6.) However, it seems doubtful that this effect would be of the magnitude required to support the requirements of rapidly proliferating malignant cells.

In addition, the literature is conflicting. Cerivastatin (taken off the market in August, 2001), inhibits endothelial cell proliferation induced by angiogenic factors in in vitro and in vivo models (Arterioscler Thromb Vasc Biol 2002 Apr 1;22(4):623-9, FEBS Lett 2001 Apr 27;495(3):159-66). Atorvastin inhibits angiognesis at high doses but has the opposite effect at low doses(Circ Res 2002 Apr 5;90(6):737-44) presumably by differing effects on geranylated proteins (Circulation 2002 Feb 12;105(6):739-45.) The possibility if not likelihood that long term statin therapy will contribute to an increased incidence of cancer is supported by numerous studies, including the CARE trial, where there were 13 cases of breast cancer cases compared to only one in the control group. Uffe Ravnskov, I and others have tried to explain this concern with extensive additional documentation in joint and individual letters to BMJ and Lancet without success. There may be valid reasons for these repeated rejections but the realization that advertising revenues from statin manufacturers may play a role has led to a certain degree of paranoia, and there is nothing worse than being paranoid and being right.

Paul J. Rosch, M.D., F.A.C.P.
President, The American Institute of Stress
Clinical Professor of Medicine and Psychiatry
New York Medical College

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