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

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. 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). 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: 1.3192-2.4894, P < .001). These results were consistent with the weighted median algorithm (OR: 1.9638, 95% CI: 1.2686-3.0399, P = .002). Furthermore, the results from GSMR were also consistent with the above results (OR: 1.7099, 95% CI: 1.2632-2.3144, P < .001). Elevated H pylori OMP antibody levels are associated with increased pancreatic cancer risk. OMP may serve as a potential vaccine target for future prevention strategies.