A two-sample Mendelian randomization study of the causal relationship between respiratory diseases, gastric cancer risk, and Helicobacter pylori infection

BACKGROUND: Gastric cancer is a major global burden, yet evidence linking respiratory diseases to gastric cancer is limited. This study examined whether genetic susceptibility to respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung diseases due to external agents (LDEA) was associated with gastric cancer and Helicobacter pylori infection, given shared immune and inflammatory pathways. METHODS: We conducted a two-sample Mendelian randomization analysis using genetic variants as instrumental variables to assess causal associations between respiratory diseases and risk of gastric cancer and H. pylori infection. GWAS summary statistics for respiratory diseases were obtained from FinnGen, and for gastric cancer and H. pylori infection from the UK Biobank. Analyses were adjusted for confounders such as smoking and alcohol consumption. Sensitivity analyses evaluated robustness and assessed potential pleiotropy and heterogeneity among genetic variants. RESULTS: No significant direct causal associations were found between respiratory diseases and gastric cancer risk. However, asthma and LDEA were significantly associated with increased risk of H. pylori infection. No associations were observed for COPD or IPF with either outcome. Sensitivity analyses indicated minimal pleiotropic or heterogeneity effects. CONCLUSION: This study investigated genetic susceptibility to respiratory diseases and their potential links to gastric cancer and H. pylori infection. While direct genetic evidence linking respiratory disease susceptibility to gastric cancer was limited, significant associations with H. pylori infection suggest possible indirect pathways involving respiratory diseases.