Education as a protective factor against lung cancer: A comprehensive Mendelian randomization analysis

Lung cancer remains a leading cause of global morbidity and mortality, imposing a significant healthcare burden worldwide. To comprehensively investigate potential risk factors for lung cancer and provide a theoretical basis for its prevention and treatment, we utilized publicly available genome-wide association study data of European ancestry. We treated various traits as exposures and lung cancer as the outcome. Causal relationships were assessed using 5 Mendelian randomization (MR) methods: inverse-variance weighted, constrained maximum likelihood and model averaging, debiased inverse-variance weighted, contamination mixture, and Mendelian randomization-robust adjusted profile score. We subsequently performed meta-analysis and median-based MR to synthesize the roles of different risk factors in lung cancer development. Following outlier removal via radial MR and MR analyses, we identified 88, 113, 248, and 232 exposure datasets showing causal associations with lung adenocarcinoma, small cell lung cancer, lung cancer overall, and squamous cell lung cancer, respectively. Further integration via meta-analysis and median MR revealed that higher educational attainment may reduce lung cancer risk by delaying age at first sexual intercourse, increasing age at first childbirth, lowering body mass index and adiposity, and reducing smoking frequency. Our comprehensive analysis suggests that education may play a protective role against lung carcinogenesis, potentially mediated through behavioral changes such as reduced smoking and modifications in physical health indicators including body mass index and adiposity.