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



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.



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.



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 long-term smoking cessation, an elevated risk of bladder cancer remains.
Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands, Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands, f.vanosch@maastrichtuniversity.nl.
Frits Hm
FH
van Osch
Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Sylvia Hj
SH
Jochems
Department of Pharmacology and Toxicology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands and.
Frederik-Jan
FJ
van Schooten
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
Richard T
RT
Bryan
Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK, Department of Complex Genetics, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, The Netherlands.
Maurice P
MP
Zeegers
D005260:Female; D006801:Humans; D008297:Male; D064887:Observational Studies as Topic; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D016540:Smoking Cessation / Q000379:methods; D013997:Time Factors; D000073869:Tobacco Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000209:etiology*
Bladder cancer incidence; dose-response analyses; meta-analysis; observational studies; population-attributable risk; smoking