Associations Between Gastroenteropancreatic Neuroendocrine Neoplasms and Inflammatory Factors: Insights From a Two-Sample Mendelian Randomization Analysis.

Purpose: Inflammation is implicated in the pathogenesis of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs); however, the causal nature of this association remains unclear. This study sought to evaluate the causal relationships between GEP-NENs and inflammatory factors using a two-sample Mendelian randomization (MR) approach. Methods: We performed a two-sample MR analysis to investigate the causal associations between 91 inflammatory proteins and 731 immune cell traits as exposures and the five subtypes of GEP-NENs as the outcomes. The analytical approach employed various methodologies, such as inverse variance weighting, MR-Egger, weighted mode, weighted median, and simple mode. To evaluate the robustness of the results, sensitivity analyses were conducted, which encompassed MR Egger regression, MR multiple gene residual and outlier detection, leave-one-out analysis, and Cochran's Results: After FDR correction, the findings revealed robust causal associations between genetically predicted HLA DR++ monocyte %leukocyte (OR = 3.09, 95% CI: 1.76-5.44, Conclusion: These findings reveal the immune mechanisms underlying GEP-NENs and highlight potential therapeutic strategies targeting the immune microenvironment of GEP-NENs.