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May 15, 1996

Carcinogenicity of Lipid-Lowering Drugs

Author Affiliations

Chemical Industry Institute of Toxicology Research Triangle Park, NC

JAMA. 1996;275(19):1479. doi:10.1001/jama.1996.03530430023025

To the Editor.  —The recent article by Drs Newman and Hulley1 suggests that rodent hepatocarcinogenicity of fibrate drugs such as gemfibrozil indicates increased risk of cancer in patients on long-term, preventive therapy for coronary heart disease (CHD). However, the mechanism of rodent hepatocarcinogenicity for fibrates is not predictive of human cancer risk.Fibrates produce striking adaptive changes in rodent liver following oral administration, including hepatomegaly, hyperplasia, increased hepatocellular peroxisomal volume, and enzyme induction.2 These drugs and most (perhaps all) so-called peroxisome proliferators do not cause mutations. Rather, their carcinogenic activity has been attributed to the adaptive effects described above, notably the modulation of cell proliferation and the induction of H2O2-producing, peroxisomal fatty acyl coenzyme A oxidase (ACO) activity in hepatocytes. In rodent studies in which incidence of liver tumors is increased, it is usual to observe a doubling of absolute liver weights and at