Gastric Mucosal Molecular Alterations and Multimodal Field-Based Risk Models for Gastric Cancer Development

Gastric cancer risk involves Helicobacter pylori infection, lifestyle and environmental exposures, host susceptibility, and precancerous mucosal changes, such as atrophy and intestinal metaplasia. Although clinical, endoscopic, and histological findings underpin current risk stratification, outcome heterogeneity persists among individuals with similar phenotypes. Here, we review evidence supporting the gastric "multimodal field" as an additional risk assessment layer, emphasizing inflammation- and exposure-associated DNA methylation as a scalable biomarker of field cancerization. Prospective studies and deep profiling of high-risk intestinal metaplasia support methylation-based field cancerization. In a longitudinal health check-up cohort, our work supports an integrated approach combining methylation markers with routinely available clinical variables. We discuss near-term multimodal extensions that may improve interpretability and predictive precision and support more effective personalized surveillance strategies.