Genetic Susceptibility to Helicobacter pylori Infection and Pancreatic Cancer Risk: A Two-Sample Mendelian Randomisation Study

TL;DR

This study used genetic data to investigate whether Helicobacter pylori infection causes pancreatic cancer, finding no significant link.

Contribution

The study applies two-sample Mendelian randomisation to assess a potential causal relationship between H. pylori and pancreatic cancer.

Findings

No significant causal association was found between H. pylori infection and pancreatic cancer risk.

Multiple MR methods confirmed null results with no strong evidence of pleiotropy.

Results suggest the need for larger studies with refined exposure measures.

Abstract

Background/Objectives: Pancreatic cancer is one of the most lethal malignancies, with poor survival and few established modifiable risk factors. While Helicobacter pylori (H. pylori) infection is a known cause of gastric cancer, its role in pancreatic cancer remains unclear, with inconsistent observational evidence. Methods: We applied two-sample Mendelian randomisation (2SMR) to assess the causal effect of H. pylori infection on pancreatic cancer risk. Genetic instruments were derived from GWAS data on anti-H. pylori IgG levels in the ALSPAC cohort (n = 4638). Outcomes were pancreatic cancer cases from UK Biobank (936 cases, 400,294 controls) and a combined dataset including UK Biobank, FinnGen, and MVP (5979 cases, 1,234,860 controls). Inverse-variance weighted (IVW) MR was the primary method, supported by MR-Egger, weighted median/mode and MR-PRESSO, with sensitivity analyses for pleiotropy. Results: No significant causal association was observed. IVW ORs were 1.039 (95% CI: 0.846–1.440, p = 0.466) for UK Biobank and 1.077 (95% CI: 0.962–1.206, p = 0.197) for the combined dataset. All complementary methods yielded null results, with no strong evidence of pleiotropy. Conclusions: This 2SMR study found no evidence that H. pylori infection causally increases pancreatic cancer risk. Larger studies with refined exposure measures are warranted.

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