Genomic epidemiology of Helicobacter pylori in regions with high and low risk of gastric cancer, Colombia

Background Helicobacter pylori infects more than half of the world’s population and is the main risk factor for gastric cancer, although only a small percentage of those infected develop the disease. This disparity suggests the influence of bacterial, environmental, and host susceptibility factors. In Colombia, the department of Nariño presents a unique scenario: in both the Andean region and the Pacific coast, the prevalence of infection reaches 90%, but gastric cancer rates differ markedly (150/100,000 and 6/100,000 inhabitants, respectively), a phenomenon known as the “Colombian enigma.” Methods This study analyzed gastric cancer mortality in 64 municipalities in Nariño, Colombia, using official epidemiological data and genome-based Helicobacter pylori cagA and vacA evolution and virulence. Results The results showed a positive correlation between altitude and gastric cancer mortality. Phylogenomically, two local subpopulations were identified: hspColombia_Andes, predominant in high-risk areas and hspColombia_PacificCoast, associated with low risk. These populations showed genetic overlap, reflecting flow between nearby regions. Conclusions Our findings show that the genetic diversity of Helicobacter pylori , particularly the hspColombia_Andes and hspColombia_PacificCoast subpopulations, is associated with regional differences in gastric cancer mortality. Furthermore, the influence of environmental factors such as altitude and the association of the vacA and cagA oncogenes with gastric lesions reinforce their role in pathogenesis and in the possible prediction of cancer risk.