Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis.

Educational attainment (EA) has been linked to the risk of several types of cancer, despite having no expected direct biological connection. In this paper, we investigate the mediating role of alcohol consumption, smoking, vegetable consumption, fruit consumption and body mass index (BMI) in explaining the effect of EA on 7 cancer groupings. Large-scale genome wide association study (GWAS) results were used to construct the genetic instrument for EA and the lifestyle factors. We conducted GWAS in the UK Biobank sample in up to 335,024 individuals to obtain genetic association data for the cancer outcomes. Univariable and multivariable two-sample Mendelian randomization (MR) analyses and mediation analyses were then conducted to explore the causal effect and mediating proportions of these relations. MR mediation analysis revealed that reduced lifetime smoking index accounted for 81.7% (49.1% to 100%) of the protective effect of higher EA on lower respiratory cancer. Moreover, the effect of higher EA on lower respiratory cancer was mediated through vegetable consumption by 10.2% (4.4% to 15.9%). We found genetic evidence that the effect of EA on groups of cancer is due to behavioural changes in avoiding well established risk factors such as smoking and vegetable consuming.

1,331 British ancestry cases, 334,378 British ancestry controls