Association of socioeconomic status and nine modifiable lifestyle factors on esophageal cancer risk in European and East Asian populations - Evidence from a comprehensive Mendelian randomization study.

Background and aims: the intricate relationships between socioeconomic factors, modifiable lifestyle choices, and esophageal cancer risk remain uncertain. We aim to investigate the associations of socioeconomic status, modifiable lifestyle factors, and esophageal cancer risk. Methods: we employed multiple Mendelian randomization (MR) analyses, including three different MR approaches. GWAS databases from European and East Asian populations, encompassing variables such as household income, educational attainment, and the Townsend deprivation index (TDI), were analyzed. The risk of esophageal cancer was assessed using data from three distinct cohorts of European and East Asian descent (Database 1: n = 476,306; Database 2: n = 372,756; Database 3: n = 160,589). Nine modifiable lifestyle factors were incorporated in the multivariable and mediation MR analyses. Meta-analysis was employed to synthesize results across the three datasets. Results: higher household income was connected with a reduced esophageal cancer risk (odds ratio (OR) = 0.698, 95 % confidence interval (95 % CI): 0.556-0.876, p = 0.002). Body mass index (BMI) partially mediated the relationship between household income and the risk of esophageal cancer (OR = 0.914, 95 % CI: 0.841-0.992, p = 0.031, mediation ratio: 27.23 %). However, no significant evidence was found to support a direct association between educational attainment, TDI, and esophageal cancer risk. Conclusions: these findings suggest that higher household income is inversely associated with esophageal cancer risk, with BMI acting as a partial mediator of this relationship. Accordingly, targeted early screening and preventive measures for esophageal cancer should be prioritized among low-income populations, particularly those with obesity.