Education and lung cancer: a Mendelian randomization study

Background: We aimed to investigate whether more years spent in education are causally associated with a lower risk of lung cancer, through a two-sample Mendelian randomization study. Methods: The main analysis used publicly available genetic summary data from two large consortia [International Lung Cancer Consortium (ILCCO) and Social Science Genetic Association Consortium (SSGAC)]. Genetic variants used as instrumental variables for years of education were derived from SSGAC. Finally, genetic data from three additional consortia (TAG, GLGC, GIANT) were analysed to investigate whether education could causally alter common lung cancer risk factors. The exposure was the genetic predisposition to higher levels of education, measured by 73 single nucleotide polymorphisms from SSGAC. The primary outcome was the risk of lung cancer (11 348 events in ILCCO). Secondary outcomes based on different histological subtypes were also examined. Analyses were performed using the package TwoSampleMR in R. Results: Genetic predisposition towards 3.6 years of additional education was associated with a 52% lower risk of lung cancer (odds ratio 0.48, 95% confidence interval 0.34 to 0.66; P = 1.02 x 10 - 5). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely. The Mendelian randomization assumptions did not seem to be violated. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index and a favourable blood lipid profile. Conclusions: Our study indicated that low education is a causal risk factor in the development of lung cancer. Further work is needed to elucidate the potential mechanisms.