Use of bidirectional Mendelian randomization to unveil the association of Helicobacter pylori infection and Pancreatic cancer

Abstract Introduction: Helicobacter pylori(H. pylori), a common gram-negative bacterium and known carcinogen, causes chronic infection. Recent studies suggest its link to extra-gastric cancers, including pancreatic cancer, but conflicting findings due to confounding factors hinder clear association. Methods: Using summary-level data from genome-wide association studies, we analyzed the bidirectional causal relationship between H. pylori-related antibody-mediated immune responses and pancreatic cancer. We further validated the results using generalized summary-data-based Mendelian randomization(GSMR). Results: We found that the levels of H. pylori outer membrane protein(OMP) antibody can significantly increase the risk of pancreatic cancer (OR: 1.8122, 95% CI: 1.3192 to 2.4894, P < 0.001). These results were consistent with the weighted median algorithm (OR: 1.9638, 95% CI: 1.2686 to 3.0399, P = 0.002). Furthermore, the results from GSMR were also consistent with the above results (OR: 1.7099, 95% CI: 1.2632 to 2.3144, P < 0.001). Conclusion: Our study found that H. pylori OMP antibody levels significantly increase pancreatic cancer risk. With rising antibiotic resistance, OMP’s adhesive properties and immune-triggering potential make it a promising target for H. pylori vaccine development, offering future prospects for prevention and treatment.