Background & Objective: Interactions between Helicobacter pylori (H. pylori) and the human host particularly gastric inflammation and cytokine-mediated signaling have been extensively investigated due to their critical role in the pathogenesis of gastric disorders. This study aimed to evaluate the association between IL1B gene polymorphisms and the risk of chronic gastritis and gastric cancer in H. pylori–infected individuals from Northwestern Iran, a region with a considerable burden of gastric disease.
 Materials & Methods: A total of 210 participants were enrolled and stratified into three groups: healthy controls, patients with chronic gastritis, and patients with gastric cancer (70 individuals per group). Peripheral blood samples collected in EDTA tubes were used for serological detection of H. pylori using an ELISA assay (Pishtaz Teb diagnostic kit) and for genomic DNA extraction. Genotyping of IL1B polymorphisms at positions −31, −511, and +3954 was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis.
Results:  Of the 210 participants, only seven individuals in the gastritis group were positive for H. pylori. The CT genotype of IL1B −31 was more frequently observed in H. pylori–negative patients with gastritis. At the IL1B −511 locus, the CC genotype was significantly more prevalent among H. pylori negative healthy controls, suggesting a protective effect against gastritis (p = 0.023). Additionally, the combined CT+TT genotypes at this locus were significantly associated with gastritis in H. pylori positive individuals (p = 0.010). No significant associations were detected between the IL1B +3954 polymorphism and disease status or H. pylori infection.
Conclusion:  These findings demonstrate a significant association between IL1B gene polymorphisms and susceptibility to chronic gastritis and gastric cancer, particularly in the context of H. pylori infection. Further large-scale studies across diverse populations are warranted to elucidate the contribution of host genetic factors to gastric disease risk.