Association between coffee consumption and risk of bladder cancer in a meta-analysis of 16 prospective studies

Abstract Background Current evidence remains equivocal as to whether and how consumption of coffee may be associated with risk of bladder cancer, and potential influence of confounding by smoking on this association is yet to be elucidated. We conducted an updated meta-analysis of prospective studies to address these issues. Methods Relevant studies were identified by searching PubMed and EMBASE databases from inception to April 2019. A random-effects model was used to estimate summary relative risk (RR) with corresponding 95% confidence interval (CI) of bladder cancer associated with coffee consumption. Results The final analysis included 16 prospective studies comprising 2,122,816 participants and 11,848 bladder cancer cases. Overall, coffee consumption was not associated with risk of bladder cancer (RR high-vs-low = 1.07, 95% CI: 0.96–1.20). The lack of association persisted in the strata defined by sex or participants’ smoking status. Meta-regression analyses identified the number cases (P difference = 0.06) and the degree of adjustment for smoking (P difference = 0.04) as potential sources of heterogeneity. There was an increased risk of bladder cancer related to higher coffee consumption among studies with fewer cases (RR high-vs-low = 1.38, 95% CI: 1.05–1.81) and among those with poorer adjustment for smoking (RR high-vs-low = 1.48, 95% CI: 1.14–1.93). Results were similar in the dose-response analyses (RR 1 cup/d = 1.01, 95% CI: 0.98–1.03). Conclusion Best evidence available to date does not support an independent association between coffee consumption and bladder cancer risk. Some direct associations observed in individual studies may be a result of residual confounding by smoking.