Quantified relations between exposure to tobacco smoking and bladder cancer risk: a meta-analysis of 89 observational studies

Background: Smoking is a major risk factor for bladder cancer (BC). This meta-analysis updates previous reviews on smoking characteristics and BC risk, and provides a more quantitative estimation of the dose-response relationship between smoking characteristics and BC risk. Methods: In total, 89 studies comprising data from 57 145 BC cases were included and summary odds ratios (SORs) were calculated. Dose-response meta-analyses modelled relationships between smoking intensity, duration, pack-years and cessation and BC risk. Sources of heterogeneity were explored and sensitivity analyses were conducted to test the robustness of findings. Results: Current smokers (SOR = 3.14, 95% CI = 2.53-3.75) and former smokers(SOR = 1.83, 95% CI = 1.52-2.14) had an increased risk of BC compared with never smokers. Age at first exposure was negatively associated with BC risk. BC risk increased gradually by smoking duration and a risk plateau at smoking 15 cigarettes a day and 50 pack-years was observed. Smoking cessation is most beneficial from 20 years before diagnosis. The population-attributable risk of BC for smokers has decreased from 50% to 43% in men and from 35% to 26% in women from Europe since estimated in 2000. Results were homogeneous between sources of heterogeneity, except for lower risk estimates found in studies of Asian populations. Conclusions: Active smokers are at an increased risk of BC. Dose-response meta-analyses showed a BC risk plateau for smoking intensity and indicate that even after longterm smoking cessation, an elevated risk of bladder cancer remains.