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Thiazolidinediones and the Risk of Lung, Prostate, and Colon Cancer in Patients With Diabetes

Rangaswamy Govindarajan, Luke Ratnasinghe, Debra L. Simmons, Eric R. Siegel, Madhu V. Midathada, Lawrence Kim, Peter J. Kim, Randall J. Owens, Nicholas P. Lang

From the Central Arkansas Veterans Health Care System; and the University of Arkansas for Medical Sciences, Little Rock, AR

Address reprint requests to Rangaswamy Govindarajan, MD, MRCP (United Kingdom) University of Arkansas for Medical Sciences, 4301 West Markham, Slot 508, Little Rock, AR 72205; e-mail: govindarajanrang{at}uams.edu

Purpose Peroxisome proliferator-activated receptor gamma (PPAR) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)^min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted.

Patients and Methods Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents).

Results Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance.

Conclusion TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.

Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-15, 2005, Orlando, FL.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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