Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study

BACKGROUND: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. METHODS: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane’s Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. RESULTS: In the MR analysis, we found Crohn’s disease had a significant causal effect on pancreatic cancer. Specifically, Crohn’s disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. CONCLUSION: This study indicates that IBD, particularly Crohn’s disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.