Pancreatic cancer risk after acute and chronic pancreatitis: Evidence from Mendelian randomization and meta-analysis

Pancreatitis may be associated with the risk of developing pancreatic cancer (PC). Previous retrospective studies have shown that chronic pancreatitis (CP) may increase the risk of pancreatic cancer. However, the causal relationship between acute pancreatitis (AP) and pancreatic cancer remains unclear. We performed Mendelian randomization (MR) analysis to investigate the causal relationship between AP and PC and validate the effect of CP on PC identified in previous retrospective studies. Genome-wide association study data for AP, CP and PC were obtained from a public database. Inverse-variance weighting is the most important MR method for analyzing causality. Sensitivity analysis was used to evaluate the robustness of MR. Finally, a meta-analysis based on the inverse-variance weighting results was conducted to strengthen the robustness of the MR further. Four MR analyses were performed to investigate the effect of AP on PC. There was a result showing AP decreased the risk of PC (odds ratio [OR]: 0.773, 95% confidence interval [CI]: 0.612-0.975, P = .030), but other 3 results were not statistically significant (P > .05). The results of the meta-analysis revealed that AP did not increase the risk of PC (OR: 0.941, 95% CI: 0.861-1.029, P = .182). Three MR analyses were performed to validate the effect of CP on PC. There was a result showing CP increased the risk of PC (OR: 1.208, 95% CI: 1.037-1.406, P = .015), but the other 2 results were not statistically significant (P > .05). The results of the meta-analysis revealed CP increased the risk of PC (OR: 1.079, 95% CI: 1.011-1.152, P = .023). We confirmed that CP is associated with a greater risk of PC. However, there is no direct causal relationship between AP and PC. More clinical and experimental studies are needed to investigate the causal relationship.