Bidirectional and mediation Mendelian randomization of dietary intake and risks of gastric ulcer and gastric cancer

Epidemiological studies have suggested associations between dietary intake and gastric ulcer (GU) or gastric cancer (GC), but the causal relationships remain unclear. This study aimed to clarify these links using bidirectional and mediation Mendelian randomization (MR) analysis. We used genome-wide association study data for 226 dietary factors as exposures and GU and GC as outcomes, derived from the FinnGen database (7012 GU cases, 385,082 controls; 1423 GC cases, 345,118 controls). Single nucleotide polymorphisms were selected as instrumental variables. MR analyses were performed using inverse variance weighted, MR-Egger regression, weighted median, and weighted mode methods. Heterogeneity and pleiotropy were evaluated with Cochran Q , I ² statistics, MR-Egger regression, and leave-one-out analysis. Mediation MR analysis was conducted to investigate the role of 1400 metabolites in mediating dietary effects on GC. MR analysis indicated that average weekly beer plus cider intake and hard cheese intake were positively associated with GU, whereas average monthly red wine intake, cereal intake, courgette intake, dried fruit intake, other egg intake, seeds intake, and spinach intake were negatively associated. GU appeared to influence dietary choices, decreasing cheesy biscuits, oily fish, and yogurt consumption, while increasing poultry, pulses, and sweet potato intake. For GC, instant soup and milk-based puddings were positively associated, while oily fish, hot soup, red wine, pineapple, sweetener-added cereal, and water were negatively associated. Reverse mediation MR analysis showed no significant effect of GC on different food intakes. Mediation analysis suggested that the effect of other meat intake on GC was partially mediated through salicylate (15.09%) and carotene diol (13.10%) levels. This study reveals the complex relationships between different dietary intakes and GU and GC through bidirectional and mediation MR. These findings suggest that dietary modification and metabolite regulation may hold potential as preventive or therapeutic strategies for GU and GC.