The association between celiac disease and digestive system cancers: A Mendelian randomization study.

Abstract

Background Relevant studies have shown a causal relationship between celiac disease and digestive system cancers risk. However, the causal relationship is controversial. Therefore, we aimed to investigate whether CD is causally associated digestive system cancers, including colorectal cancer, Gastric cancer, Oesophageal Cancer, Small intestine cancer, Hepatic cancer, Pancreatic cancer, and Gallbladder cancer using an mendelian randomization (MR) approach.Methods We conducted analyses using two sets of instrumental variables in a two-sample MR design. Summary-level data for colorectal cancer, gastric cancer, oesophageal cancer, Small intestine cancer, Hepatic cancer, Pancreatic cancer, and Gallbladder cancer were obtained from genome-wide association analyses of the UK Biobank study. Summary-level data for celiac disease was derived from a genome-wide association study conducted in the UK Biobank population. We calculated the causal effect using the inverse variance weighted method. Sensitivity analyses and leave-one-out analyses were performed to ensure the consistency and robustness of causal estimates.Results IVW analysis showed a positive causal relationship between CD and CRC risk (OR = 1.106, 95%CI: 1.043–1.173, p < 0.001). In reverse Mendelian randomization, we found that: colorectal cancer is not causally related to celiac disease(OR = 0.968, 95%CI: 0.913–1.027, p = 0.276). IVW analysis demonstrated that CD didn’t have causal association with the other digestive tract cancers (Gastric cancer :OR = 0.220, 95%CI:4.12E-5-1.180E + 3, p = 0.730; Oesophageal cancer: OR = 0.997, 95%CI: 0.986–1.007, p = 0.089; Small intestine cancer: OR = 1.017, 95%CI: 0.998–1.036, p = 0.547; Hepatic cancer: OR = 0.053c, 95%CI: 2.28E-10-1.236E + 7, p = 0.770; pancreatic cancer: OR = 40.763, 95%CI: 0.011-1.492E + 5, p = 0.376; Gallbladder cancer: OR = 169.240, 95%CI: 1.90E-68-1.51E + 72, p = 0.950). No evidence of horizontal pleiotropy was identified (MR Pleiotropy Residual Sum and Outlier global test and MR-Egger intercept with P > 0.05). The leave-one-out sensitivity analyses revealed that the causal estimates were not disproportionately influenced by any individual SNP.Conclusion Our findings suggest that coeliac disease was positively associated with the risk of colorectal and colon cancer, but not causally associated with Gastric cancer, Oesophageal Cancer, Small intestine cancer, Hepatic cancer, Pancreatic cancer, and Gallbladder cancer.