Background: Gastric cancer shows striking geographic heterogeneity in the northern Andes. Nariño (Colombia) became a natural model of high risk where decades of multidisciplinary research contributed to the formulation and validation of the Correa cascade—an ordered histopathological sequence from chronic active gastritis to multifocal atrophy, intestinal metaplasia, dysplasia, and invasive adenocarcinoma. This integrative review synthesizes more than five decades of evidence generated in Nariño and related Colombian populations and updates the conceptual framework of gastric carcinogenesis by incorporating contemporary insights on host susceptibility, bacterial diversity, and host–pathogen coevolution, with explicit implications for cancer prevention.

Methods: We conducted an integrative review of epidemiological, endoscopic, histopathological, clinical, microbiological, immunological, and genetic studies performed in high-risk Andean settings and in contrasting low-risk coastal populations. Evidence was organized around three axes: (i) the natural history of the precancerous sequence and its dynamic progression and regression; (ii) determinants of geographic risk contrasts, including dietary salt intake, consumption of fresh fruits and vegetables, bacterial virulence profiles, immune polarization, and helminth co-infections; and (iii) randomized chemoprevention strategies and long-term follow-up after Helicobacter pylori eradication, emphasizing durability of effects.

Results: Across high-risk populations, atrophy and intestinal metaplasia were frequent and often extensive, with a slow but persistent tendency to progress, punctuated by partial regressions consistent with a “steady state” process. Randomized interventions demonstrated that sustained H. pylori eradication is associated with significant and cumulative regression of precursor lesions, most pronounced when treatment occurs at earlier stages of the cascade. In contrast, antioxidant supplementation showed benefits largely limited to the period of intake, with little evidence of durable residual effects after discontinuation. Marked risk contrasts between Andean and coastal populations were not explained by infection prevalence alone, but by a broader interaction of bacterial virulence profiles, host inflammatory responses, diet, and helminth-associated Th2 immune modulation. Integration of evolutionary biology adds a unifying mechanism: disruption of host–H. pylori coevolution, reflected by mismatches between human ancestry and bacterial lineages, may amplify inflammatory damage and accelerate progression along the Correa cascade, offering a robust explanation for sharp geographic disparities in gastric cancer risk.

Conclusions: Expanding the Correa cascade to incorporate coevolutionary dynamics provides a prevention-oriented framework that translates research into action. Aligned with IARC priorities, this approach supports implementable prevention packages for high-risk Andean populations, including test-and-treat strategies with verified long-term cure, simplified risk stratification based on host susceptibility and bacterial lineage or virulence, and endoscopic surveillance focused on individuals with advanced precursor lesions. Complementary population-level measures, such as dietary salt reduction and improved access to fresh foods, address feasibility and equity. Together, these components support scalable, evidence-based gastric cancer prevention policies adaptable across heterogeneous Latin American settings and evaluable through measurable intermediate endpoints, including regression of atrophy and intestinal metaplasia and reduction of advanced precursor lesions.