Abstract
BACKGROUND: Hitherto, the association of vitamin D intake and digestive system cancers occurrence still causes disputation among the researchers. This study aimed to investigate the genetic relation between vitamin D ingestion and digestive system cancers (which are esophageal, gastric, hepatic, pancreatic, and colorectal cancers) by a two-sample Mendelian randomization (MR) analysis, using datasets derived from IEU OpenGWAS database. METHODS: This study is based on a genome-wide association study (GWAS) for vitamin D and digestive system cancers, with a sample amount ranging from 218,792 to 496,946 European ancestry individuals. The study first investigated the causal relationship between vitamin D and each digestive system cancers using inverse-variance weighting (IVW), weighted medians, and MR-Egger regression and then used meta-analysis to summarize the IVW results for the different cancers. We also performed additional sensitivity tests to assess the validity of the results. RESULTS: In this study, we screened out 117 SNPs as potential instrumental variables for 25(OH)D and identified 101 fixed SNPs as instrumental variables for digestive system cancers. The results of the IVW failed to reveal any causal relationship between the genetically predisposed vitamin D level and the risk of digestive system cancers (esophageal cancer p = 0.400, OR = 1.397, 95% CI 0.642-3.040; gastric cancer p = 0.796, OR = 0.939, 95% CI 0.585-1.510; hepatic cancer p = 0.347, OR = 1.445, 95% CI 0.671-3.109; pancreatic cancer p = 0.905, OR = 0.969, 95% CI 0.581-1.618; colorectal cancer p = 0.127, OR = 0.0.841, 95% CI 0.673-1.051). The pooled ORs (odds ratio) are 0.918 (95% CI 0.770-1.097, p = 0.348). CONCLUSION: There is no causal relationship between vitamin D and the occurrence of digestive system cancers. The risk of digestive system cancers cannot be alleviated by merely increasing vitamin D intake.