Abstract: Objective To provide new clues for the prevention and treatment of digestive system malignancies by using two sample Mendelian randomization(TSMR)method so as to explore the causal relationship between metabolic syndrome(MetS)and its components and digestive system malignancies from a genetic perspective. Methods Based on the summary data of genome-wide association study(GWAS), MetS and its components were used as exposure factors, and digestive system maligancies were used as outcome variables. The inverse variance weighted(IVW)method was used as the main analysis method, and weighted median(WM)and MR Egger were used as supplementary analysis methods to evaluate causal effects. The sensitivity analysis was used to verify the reliability of the research results. Results The IVW method showed that MetS is associated with an increased risk of liver cancer(OR=1.357, 95%CI=1.004-1.834, P=0.047)and esophageal cancer(OR=1.001, 95%CI=1.000-1.001, P=0.037). Among the components of MetS, waist circumference(WC)is associated with an increased risk of gastric cancer(OR=1.809, 95%CI=1.024-3.196, P=0.041)and esophageal cancer(OR=1.001, 95%CI=1.000-1.002, P=0.020); High density lipoprotein(HDL)is associated with a reduced risk of colorectal cancer(OR=0.789, 95%CI=0.633-0.984, P=0.035); Sensitivity analysis suggests that the research results are robust. Conclusion MetS increases the risk of liver and esophageal cancer, with WC being a risk factor for gastric and esophageal cancer, while HDL is a protective factor for colorectal cancer.

Key words: Mendelian randomization, Metabolic syndrome, Digestive system malignancies, Genome wide association study, Causal association