Bladder cancer risk factors: a comprehensive umbrella review of meta-analyses

Bladder cancer represents a significant global health challenge, characterized by poorly understood risk factors. This study aims to synthesize meta-analytical evidence, quantify risk associations, and inform prevention strategies.

We conducted a comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library up to October 2024. Meta-analysis quality was assessed using AMSTAR 2, and evidence certainty was evaluated via the GRADE approach. To explore heterogeneity and enhance interpretation, we conducted subgroup analyses for 23 exposure-outcome associations.

Eighty-four meta-analyses assessing 156 risk factors were included; 79 reported potential associations with bladder cancer. These covered dietary (n = 23), disease-related (n = 20), medication (n = 10), environmental and lifestyle (n = 9), occupational (n = 13), and physiological (n = 4) factors. The GRADE system rated 60 potentially associated outcomes as very low quality, 16 as low quality, and 3 as moderate quality. Moderate-certainty evidence identified ANCA-associated vasculitis (AAV) (RR = 3.84), opium consumption (RR = 4.07), and particulate matter with a diameter of 2.5 micrometers or less (PM2.5) exposure (RR = 1.07) as risk factors. Dose-response analyses revealed increased risk with processed meat (50 g/day), red meat (100 g/day), liquor or spirits (12 g/day), and with each 5 μg/m 3 rise in PM2.5 or 10 μg/m 3 rise in nitrogen dioxide (NO 2 ). Cruciferous vegetable intake (≥412.5 g/week) was associated with reduced risk.

This review identifies several modifiable, dose-responsive risk factors for bladder cancer and highlights areas supported by higher-certainty evidence. These findings may assist in guiding prevention efforts - such as reducing red and processed meat intake, improving air quality, and monitoring high-risk medication to help lower the burden of bladder cancer.