Vitamin D and Bladder Cancer Risk: An Umbrella Review and Second Order Meta‐Analysis

Introduction: Bladder cancer is a common malignancy with a high recurrence rate, posing a significant public health burden. Beyond its role in bone health, vitamin D has been suggested to influence cancer risk, including bladder cancer. Aim: To evaluate the association between serum vitamin D levels, dietary intake, and supplementation with bladder cancer risk. Methods: This umbrella review included systematic reviews and meta-analyses from multiple databases, focusing on serum levels or intake of vitamin D and bladder cancer risk. Study quality was assessed using the JBI Critical Appraisal Tool. The Corrected Covered Area showed a 15.5% overlap. Considerable heterogeneity in study design, populations, and vitamin D assessment was noted. Two second-order meta-analyses were conducted for quantitative synthesis. Results: Eight studies met the inclusion criteria. Adequate serum vitamin D was generally defined as levels ≥ 30 nmol/L. Low serum vitamin D was significantly associated with increased bladder cancer risk (RR = 1.32; 95% CI: [1.27, 1.38]). Higher serum levels were linked to a non-significant risk reduction (RR = 0.86; 95% CI: [0.63, 1.16]). Evidence on dietary intake was inconsistent, with some analyses suggesting a modest protective effect, particularly when combined with specific dietary patterns. Conclusions: Low serum vitamin D is consistently associated with increased bladder cancer risk, while maintaining levels above 30 nmol/L may provide some protection. Evidence on dietary intake and supplementation remains inconclusive. Future studies should adopt standardized methods for vitamin D measurement, explore the role of free versus total vitamin D, and clarify population-specific differences to better define vitamin D's role in bladder cancer prevention.