Association between education inequality and lung cancer: a two- sample Mendelian randomization study

Abstract Background: While numerous studies have explored the correlation between educational disparities and lung cancer, the definitive determination of a causal link between these factors is still pending. This study seeks to clarify the potential causal role of educational disparities in the development of lung cancer. Methods: This study employed a two-sample Mendelian randomization (MR) analysis by using genetic data from genome-wide association studies (GWAS) to explore the hypothesized causal connection between educational attainment and lung cancer. The investigation specifically concentrated on its major subtypes: Lung Squamous Cell Carcinoma (LUSC) and Lung Adenocarcinoma (LUAD). In order to enhance our understanding and address potential confounding factors, a Multivariable MR analysis was utilized. Additionally, an advanced Two-step MR methodology was applied to clarify the biological pathways through which educational attainment might impact the risk of lung cancer. Results: This study employed the Multiplicative Random-Effect Inverse Variance Weighted (IVW-MRE) as primary method in Univariable Mendelian Randomization (UVMR) analysis. The IVW-MRE approach yielded MR estimates indicating an odds ratio (OR) of 0.153 (95% Confidence Interval [CI]: 0.125-0.186) for overall Lung Cancer (LUCA), 0.195 (95% CI: 0.154–0.246) for Lung Squamous Cell Carcinoma (LUSC), and 4.860 (95% CI: 3.584–6.589) for Lung Adenocarcinoma (LUAD). Additionally, Multivariable Mendelian Randomization (MVMR) analysis confirmed the persistent significance of educational inequalities as risk determinants. A subsequent two-step MR analysis further delineated the mediating roles of smoking, alcohol consumption, and Body Mass Index (BMI) in this association, and only found alcohol consumption has mediation effect between the two traits. Conclusion: Our findings indicate a genetic connection between educational inequality and susceptibility to lung cancer. This emphasizes the need for more extensive research to unravel the complex socio-genetic interactions involved. Importantly, these results underscore the crucial role of addressing educational disparities in the epidemiology and progression of lung cancer.