Threshold dose-response association between smoking pack-years and the risk of gallbladder cancer: A nationwide cohort study

Abstract

Background and aims: The association between smoking and gallbladder cancer (GBC) risk is unclear. We investigated the association between smoking (including pack -years) and GBC risk. We also examined the combined effects of smoking and diabetes or pre -diabetes on GBC risk.Methods: This Korean nationwide cohort study included 9,520,629 adults without cancer who underwent national health screening in 2009 and were followed-up until 2018. Multivariable Cox proportional hazards models were used to determine risk estimates after adjusting for po-tential confounders.Results: During 78.4 million person-years (mean 8.2 +/- 0.9 years) of follow-up, we identified 6066 patients with newly diagnosed GBC. Current and former smokers were associated with increased GBC risk (hazard ratio [HR], 95% confidence interval [CI]: 1.117, 1.029-1.212 and 1.105, 1.016-1.202, respectively). Smoking of 20 to <30 and >30 pack-years was indepen-dently associated with increased GBC risk compared with never smoking (HR, 95% CI; 1.241, 1.100-1.400 and 1.231, 1.107-1.370, respectively). However, smoking of <10 and 10 to <20 pack-years was not. This threshold dose-response association between smoking pack-years and GBC risk was observed regardless of the glycaemic status (all P < 0.01). Furthermore, smoking of >20 pack-years and hyperglycaemia had a synergistic effect on the GBC risk (all P < 0.01). Smokers with >20 pack-years with diabetes had the highest risk of GBC compared to never smokers with normoglycaemia (HR, 1.658; 95% CI, 1.437-1.914).Conclusions: Smoking was associated with increased GBC risk with a threshold dose-response effect for smoking pack-years. The risk of GBC increases synergistically when smoking and hyperglycaemia coexist. More individualised cancer prevention education is required to reduce GBC risk.(c) 2022 Published by Elsevier Ltd.