Feed

Objective: To assess the disease burden of esophageal cancer attributable to smoking in China and globally from 1990 to 2021 and to explore the causal association between smoking and esophageal cancer. Methods: Data on smoking-attributable esophageal cancer deaths and disability-adjusted life years (DALYs) in China and globally from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) 2021 database. Joinpoint regression models were used to analyze temporal trends in the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR). The lifetime smoking index from the UK Biobank was used as the exposure, and summary-level data for esophageal cancer from a genome-wide association study (GWAS) were used as the outcome. Mendelian randomization (MR) analysis was performed to investigate the causal relationship between smoking and esophageal cancer. Cochran's Q test was applied to assess heterogeneity among instrumental variables (IVs); MR-Egger regression and MR-PRESSO were used to evaluate horizontal pleiotropy of IVs; and leave-one-out analysis together with funnel plots were conducted to examine the stability of the results. Results: From 1990 to 2021, the absolute numbers of smoking-attributable esophageal cancer deaths and DALYs increased in both China and globally, whereas the ASMR and ASDR decreased significantly. Joinpoint analysis showed that the declines in ASMR and ASDR in China (AAPC:-1.49% and -1.87%, respectively) were faster than the corresponding global declines (-1.23% and -1.57%). The decrease was significantly more rapid in females than in males (all P<0.001). MR analysis confirmed a causal association between smoking and esophageal cancer (OR=1.004, 95%CI: 1.002-1.006, P<0.001). Cochran's Q test indicated no heterogeneity (P>0.05), and MR-Egger regression and MR-PRESSO showed no evidence of horizontal pleiotropy among the IVs (all P>0.05). Leave-one-out analysis and funnel plots demonstrated the robustness of the causal estimate. Conclusion: The disease burden of esophageal cancer attributable to smoking remains substantial in both China and globally, with declining trends in age-standardized rates; notably, the decline in China has outpaced the global average. Smoking is a causal risk factor for esophageal cancer, and males represent a high-risk group.