Causal association between tea intake and digestive system malignancies： a two-sample Mendelian randomization study

Abstract:

Objective To investigate the possible causal association between tea intake and digestive system malignancies by using the two-sample Mendelian randomization method.Methods In the genome-wide association studies（GWAS） of the European population，the single nucleotide polymorphisms（SNPs） that are strongly associated with the exposure factor of tea intake were selected as instrumental variables. The summary statistics of digestive system tumors provided by The United Kingdom Biobank were used as outcome variables，including esophageal cancer，gastric cancer，small intestine cancer，colon cancer，rectal cancer，liver cancer，and intrahepatic cholangiocarcinoma. Inverse-variance weighting（IVW） was used as the primary analytic method，and a series of analyses were performed to evaluate the reliability of the study，including heterogeneity test，pleiotropic analysis，and sensitivity analysis.Results At the genome-wide significance level（P<5×10^-8），32 independent SNPs associated with tea intake were included as instrumental variables. The IVW analysis showed that tea intake was associated with an increased risk of liver cancer or intrahepatic cholangiocarcinoma（odds ratio=1.0019，95%CI=1.0003-1.0035，P=0.020），while there was no significant association between tea intake and the development of other digestive system tumors. The research findings were not affected by pleiotropy or heterogeneity，and the sensitivity analysis verified the reliability of results.Conclusion This Mendelian randomization study shows that tea intake might be a risk factor for the increased risk of liver cancer and intrahepatic cholangiocarcinoma；however，further Mendelian randomization studies with larger sample sizes of GWAS data are still needed to verify such association.