Deciphering the Roles of Thiazolidinediones and PPARγ in Bladder Cancer
OBJECTIVE To investigate whether pioglitazone treatment of patients with type 2 diabetes mellitus was associated with an increased risk of kidney cancer. METHODS The reimbursement databases of all Taiwanese patients with type 2 diabetes who received oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006, and a total of 1,093,675 patients with type 2 diabetes were followed up for kidney cancer incidence until the end of 2009. The incidences of kidney cancer among patients who had and had not received pioglitazone, as well as among subgroups of those treated with pioglitazone (sorted by time since starting pioglitazone, duration of treatment and cumulative dose) were calculated and hazard ratios (HRs) estimated by Cox regression analysis. RESULTS Of the 1,093,675 patients, 58,172 (5.3%) had and 1,035,503 (94.7%) had not received pioglitazone, with incident kidney cancer developing in 208 (0.36%) and 3304 (0.32%) patients, respectively, and a respective incidence of 97.7 and 90.5 per 100,000 person-years. Pioglitazone and kidney cancer were not significantly associated in unadjusted (HR 1.04; 95% confidence interval (CI), 0.90-1.20), age-sex-adjusted (HR 1.09; 95% CI, 0.95-1.25), and fully adjusted (HR 1.09; 95% CI, 0.94-1.26) models. None of the dose-response parameters showed a significant trend of risk association, with all P-trends >0.10. CONCLUSIONS Pioglitazone does not affect the risk of kidney cancer.