Systematic review and meta-analysis corrected for history of smoking tobacco identifies type 1 diabetes as a possible risk factor for bladder cancer

Type 2 diabetes is an established bladder cancer risk factor, but any role of type 1 diabetes in this malignancy has remained unclear. We systematically sought, critically appraised, and quantitatively synthesized published estimates of the association between type 1 diabetes and incident bladder cancer in humans. Systematic review identified nine independent studies providing relevant data, but eight of these studies had not addressed confounding by history of smoking tobacco, a strong risk factor for bladder cancer. Therefore, in this research the quantitative synthesis of original data was implemented by meta-regression to detect and quantify residual confounding by tobacco smoking, followed by synthetic meta-analysis to combine smoking-controlled estimates. This analysis robustly identified four-fold greater occurrence of bladder cancer in those with type 1 diabetes (summary estimate 4.29 [95% confidence interval: 2.45-7.47], 9 studies). Thus, type 1 diabetes appears to be a strong risk factor for bladder cancer, and it seems likely that this association was previously obscured by strong negative confounding by smoking. Studies addressing established bladder cancer risk factors together with duration and severity of type 1 diabetes are now warranted to better understand the role of type 1 diabetes in bladder cancer etiology, and to inform the care of patients.