Abstract
BACKGROUND: The objective of this study was to determine the causal relationship between habitual alcohol consumption with meals and lung cancer. METHODS: Public genetic summary data from two large consortia [the Neale Lab and the International Lung Cancer Consortium (ILCCO)] were used for analysis. As the instrumental variables of habitual alcohol consumption with meals, data on genetic variants were retrieved from Neale Lab. Additionally, genetic data from other consortia [Global Lipid Genetics Consortium (GLGC), Tobacco, Alcohol and Genetics (TAG), Genetic Investigation of Anthropocentric Traits (GIANT)] were utilized to determine whether alcohol could causally alter some general risk factors for lung cancer. The primary outcome was the risk of lung cancer (11,348 cases and 15,861 controls in the ILCCO). The R package TwoSampleMR was used for analysis. RESULTS: Based on the inverse variance weighted method, the results of the two-sample Mendelian randomization (MR) analyses indicated that commonly consuming alcohol with meals was a protective factor, reducing lung cancer risk [odds ratio (OR) 0.175, 95% confidence interval (CI): 0.045-0.682, P=0.012]. The heterogeneity analysis revealed that the causal relationship analyses of different types of lung cancer all had low heterogeneity (P>0.05). The horizontal pleiotropic study showed that major bias was unlikely. The MR assumptions did not seem to be violated. The causal relationship analyses between habitual alcohol consumption with meals and some risk factors for cancers showed that this alcohol consumption habit was a beneficial factor for reducing body mass index (BMI) and the number of cigarettes smoked per day. CONCLUSIONS: Habitual appropriate alcohol consumption with meals is a protective factor for the development of lung cancer.