Association between the use of thiazolidinediones and the risk of cancer in diabetic patients

Abstract

1005 Background: PPARγ, a member of the super family of nuclear receptors peroxisome proliferator activated receptors (PPAR) is a member of a potential tumor suppressor pathway in colon, breast, pancreas, prostate, and lung cancers. The anti diabetic agents glitazones or thiazolidinediones (TZDs) which are PPARγ ligands have antineoplastic activity in vitro but have no proven clinical benefit. The effect of TZDs on intestinal polyposis in animal models is conflicting. A retrospective study of type 2 diabetes mellitus patients was conducted to determine whether therapy with TZDs might modify the risk of colorectal, prostate and lung cancer. Methods: The data on 127,658 male patients with diabetes mellitus treated at ten veterans affairs (VA) hospitals between 1997 and 2002 was obtained from VISN-16 database. The incidence of colorectal, lung and prostate cancers during this period was determined by using ICD-9 codes. The pharmacy data regarding the use of TZDs, insulin and other treatments, as well as dietary history was also obtained from VISN-16 database. Multi-variate logistic regression was used to assess the association between the use of TZD and the risk of colorectal, lung and prostate cancers. Results: 31509 (25%) patients were treated with TZDs. 16953(13.2%) had colorectal, prostate or lung cancer. Diabetics on TZDs were at 15% reduced risk of lung cancer and 8% increased risk of prostate cancer after adjusting for age, race, diet, insulin use and body mass index compared to those who did not use TZDs. Conclusion: TZDs appear to reduce the risk of lung cancer and appears to increase the risk of prostate cancer in our cohort of male type 2 diabetes patients. The primary limitation of our findings is the lack of smoking data. The differential effect of TZDs on different cancers needs to be further evaluated. No significant financial relationships to disclose.