Correlation Between Helicobacter Pylori Infection, Gene Methylation, and Host Genetic Polymorphisms in Gastric Cancer

This study investigated how Helicobacter pylori (Hp) infection and host genetic variations contribute to gene-specific DNA methylation patterns in the development of gastric cancer in Iraqi patients. Seven genes (CYP2E1, HIN-1, MT2A, CASP3, CDKN1A, MSH6, and EpCAM) known to play roles in inflammation, DNA repair, and apoptosis were selected for methylation analysis. A total of 67 gastric tissue samples were analyzed using Methylation-Sensitive High-Resolution Melting (MS-HRM), including samples from 30 gastric cancer patients and 37 gastritis patients (subdivided by Hp status and post-eradication treatment). Results revealed significantly higher methylation frequencies in gastric cancer, particularly for CYP2E1 (80%), CASP3 (86.7%), and EpCAM (20%), compared to gastritis. Notably, CDKN1A exhibited 100% methylation across all cases, regardless of Hp status or disease stage. Certain polymorphic genotypes, including CYP2E1 T/T and CASP3 A/A, were strongly associated with increased methylation. Post-eradication analysis showed only limited reversal of methylation in some genes, such as MSH6, EpCAM, and MT2A. These findings suggest that the combined impact of Hp infection, host genetic variation, and epigenetic silencing may contribute significantly to gastric carcinogenesis. Moreover, gene methylation patterns, particularly in CYP2E1, CASP3, and EpCAM, may serve as valuable biomarkers for early detection and risk stratification of gastric cancer in clinical practice.