Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies

Background: Increasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed a systematic review with meta-analysis to explore this relationship. Methods: We identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 29 February 2012, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model. Results: A total of 36 studies (9 case-control studies, 19 cohort studies and 8 cohort studies of patients with diabetes) fulfilled the inclusion criteria. Analysis of all studies showed that DM was associated with an increased risk of bladder cancer (the summary RR = 1.35, 95% CI 1.17-1.56, p < 0.001, I-2 = 94.7%). In analysis stratified by study design, diabetes was positively associated with risk of bladder cancer in case-control studies (RR = 1.45, 95% CI 1.13-1.86, p = 0.005, I-2 = 63.8%) and cohort studies (RR = 1.35, 95% CI 1.12-1.62, p < 0.001, I-2 = 94.3%), but not in cohort studies of diabetic patients (RR = 1.25, 95% CI 0.86-1.81, p < 0.001, I-2 = 97.4%). The RRs of bladder cancer were 1.38 (1.08-1.78) for men and 1.38 (0.90-2.10) for women with diabetes, respectively. Noteworthy, the relative risk of bladder cancer was negatively correlated with the duration of DM, with the higher risk of bladder cancer found among patients diagnosed within less than 5 years. Conclusions: These findings support the hypothesis that men with diabetes have a modestly increased risk of bladder cancer, while women with diabetes were not the case.