Contrasting serum biomarker profiles in two Colombian populations with different risks for progression of premalignant gastric lesions during chronic Helicobacter pylori infection

•Coastal Colombians have lower Helicobacter pylori-associated gastric cancer compared to the Andes despite comparable infection and gastritis.•Lesion progression was associated with significant odds ratios for serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio.•Low risk patients had elevated serum inflammatory biomarkers that reflect higher exposure to infectious diseases beyond H. pylori.•Data suggest IL-5, TFF3 and pepsinogen I/II ratios should be evaluated in combination to predict aggressive gastric histology. Colombians in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared to individuals from Tuquerres in the high Andes. This is despite nearly universal prevalence of H. pylori infection and chronic gastritis. H. pylori infection was confirmed by Steiner stain and serology using African and European-origin strains. Gastric histology and serum inflammatory biomarkers in dyspeptic Tumaco or Tuquerres patients were evaluated to predict progression of gastric lesions. H. pylori infection was nearly universal by Steiner stain and serology. IgG response to European-origin H. pylori strains were greater than African-origin. High gastric cancer-risk Tuquerres patients, compared to low-risk Tumaco, had significant odds ratios for lesion progression associated with serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio. Sensitivity and specificity for these parameters was 63.8% and 67.9%, respectively, with correctly classifying patients at 66.7%. Most odds ratios for 26 other biomarkers were significant for the town of residency, indicating an environmental impact on Tumaco patients associated with decreased lesion progression. An IL-5 association with progression of gastric lesions is novel and could be evaluated in addition to TFF3 and pepsinogen I/II ratio as a non-invasive prognostic screen. Results suggest Tumaco patients were exposed to infectious diseases beyond H. pylori such as the documented high incidence of helminthiasis and toxoplasmosis. Results support a prior recommendation to evaluate TFF3 and pepsinogen I/II together to predict aggressive gastric histology. Our data indicate IL-5 should be further evaluated as prognostic parameter.