Deciphering the Roles of Thiazolidinediones and PPARγ in Bladder Cancer
Lung cancer accounted for 13% of all cancer diagnoses in the world and there were 1.8 million new cases in 2012 . Despite a decreasing trend in men, lung cancer is increasing in women in the world . However, in Taiwan, lung cancer is increasing steadily in both sexes, representing 15% and 8% of all cancers in men and women, respectively . The most important risk factor of lung cancer is cigarette smoking, but other risk factors may include air pollution, fumes from cooking and exposure to occupational and environmental carcinogens (e.g., arsenic, asbestos, polycyclic aromatic hydrocarbons and radon etc.) . Thiazolidinedione (TZD) is a class of oral antidiabetic drugs that improve insulin resistance by targeting the peroxisome proliferator-activator receptor gamma (PPARg). In Taiwan, only rosiglitazone and pioglitazone have ever been marketed. However, rosiglitazone is now rarely used due to a potential risk of acute myocardial infarction. Human studies evaluating lung cancer risk associated with pioglitazone use are not conclusive. There are three meta-analyses investigating lung cancer risk associated with the use of TZD including pioglitazone [3–5], but the findings remain controversial. The meta-analysis including 5 observational studies by Bosetti et al. suggested a null association between TZD and lung cancer (hazard ratio: 0.90, 95% confidence interval: 0.76–1.06) . On the other hand, the meta-analysis by Colmers et al. suggested a significantly lower risk associated with TZD by including 5 observational studies (hazard ratio: 0.91, 95% confidence interval: 0.84–0.98) and a null association with pioglitazone by including 2 studies (hazard ratio: 0.95, 95% confidence interval: 0.88–1.02) . Among the 5 studies included in the meta-analysis by Bosetti et al. , 2 reported a significantly lower risk associated with the use of TZD, but these studies did not specify the drug in the TZD class. The latest meta-analysis by Nie et al. also did not specify the TZD used and estimated an overall hazard ratio of 0.92 (95% confidence interval: 0.75–1.13) from 7 studies . The present study used the reimbursement database of Taiwan’s National Health Insurance (NHI) to investigate the risk of lung cancer associated with pioglitazone use in patients with type 2 diabetes mellitus.