The inflammation-epigenetics axis in gastric cancer: Helicobacter-driven field defects, immune escape, and therapeutic frontiers.

Gastric cancer provides a clinically relevant model of the inflammation-epigenetics axis because Helicobacter pylori can drive prolonged mucosal inflammation before malignant transformation. Inflammatory signaling remodels DNA methylation, histone states, chromatin accessibility and RNA-regulatory programs, generating epigenetic field defects that may persist after bacterial eradication. Epstein-Barr virus-positive gastric cancer represents a distinct hypermethylated and immune-adapted state. We organize these processes using four coordinates: inflammatory driver, dominant epigenetic lesion, cellular compartment and reversibility. Across gastric cancer subtypes, epigenetic plasticity contributes to field cancerization, antigen-presentation loss, epithelial-mesenchymal transition, stemness and drug-tolerant persistence, while parallel reprogramming of immune and stromal compartments promotes treatment resistance. Tissue and circulating DNA methylation currently have stronger translational support than circulating non-coding RNA or m6A-based signatures, which remain investigational because of source attribution, assay standardization and validation limitations. Therapeutic translation should therefore combine removal of the sustaining inflammatory driver with biomarker-guided epigenetic priming and state-matched immune or stromal intervention. Longitudinal and externally validated studies are required to convert these mechanisms into clinically useful biomarkers and treatment strategies.