Second-hand smoke and bladder cancer risk among nonsmokers: a systematic review and a meta-analysis

Bladder cancer is the 10 th most frequently diagnosed cancer worldwide. While tobacco smoking is a well-established risk factor for bladder cancer, the association between second-hand smoke (SHS) exposure and bladder cancer remains less clear. This systematic review and meta-analysis aims to update the evidence on the association between SHS exposure and bladder cancer risk, considering sex differences and exposure settings. By combining an umbrella review and a systematic review, we identified and combined in a meta-analysis all epidemiological studies assessing the association between SHS exposure and bladder cancer risk in nonsmokers, published up until October 2023. Pooled relative risks (RRs) were calculated using random-effects models. Twelve studies (eight case-control and four cohort studies), involving approximately 1200 bladder cancer cases, were included. The overall pooled RR of bladder cancer for SHS exposure was 1.16 [95% confidence interval (CI): 0.95-1.43], with slight differences when considering exposure settings. Results show a low/moderate heterogeneity ( I2  = 38%, P  = 0.09). Stratified analyses by sex showed no differences in risk of bladder cancer by sex, with an RR of 1.35 (95% CI: 0.86-2.13) in males and 1.31 (95% CI: 0.98-1.73) in females. Higher risks were observed in studies conducted in Africa and Asia. This meta-analysis considering sex differences and different exposure settings shows an increased, despite not statistically significant, association between SHS exposure and bladder cancer risk among nonsmokers. A relatively limited number of cases and studies are currently available on the issue, thus further research with greater statistical power and improved exposure assessment is needed to better clarify the role of SHS exposure in bladder cancer development.