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  • Title: Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.
    Author: Morgan DR, Dominguez RL, Keku TO, Heidt PE, Martin CF, Galanko JA, Omofoye OA, Sandler RS.
    Journal: Clin Gastroenterol Hepatol; 2006 Sep; 4(9):1103-11. PubMed ID: 16820326.
    Abstract:
    BACKGROUND & AIMS: Inflammatory cytokine polymorphisms are associated with gastric adenocarcinoma in Helicobacter pylori-infected patients in Europe and Asia. We investigated the cytokine profile in the Latino population, specifically Honduras, a high-incidence region, and the use of the combination prevalence of H pylori and genotypes in identifying high-risk populations. METHODS: A population-based case-control study identified 170 incident gastric cancer cases and 162 healthy village controls. Interleukin (IL)-Ibeta-511, IL-1RN, IL-10-1082, and tumor necrosis factor-alpha-308 genotypes were determined. We define the combination prevalence index (CPI) as the product of H pylori and IL-1beta-511T+ genotype prevalence in healthy subjects. Medline identified gastric cancer studies to facilitate country-specific CPI calculations. RESULTS: In healthy, population-based Honduran controls, IL-1beta-511T+ prevalence was 81% (95% confidence interval, 75%-87%; CT, 57%; TT, 25%), which was among the highest reported. IL-10-1082A+ prevalence was 93% (95% confidence interval, 88%-97%), mirroring Asian populations. Seventeen percent were homozygous for both proinflammatory cytokines (TT/AA), with increased risk among cases (odds ratio, 2.6; 95% confidence intervals, 1.0-6.8). Tumor necrosis factor-alpha polymorphisms were nearly absent. Endemic H pylori infection (85%) was confirmed. Importantly, the CPI association with country incidence is highly significant (P = .0057), based on 16 global populations and Honduras. Sensitivity analysis confirms a robust CPI. CONCLUSIONS: The CPI, based on IL-1beta genotypes, has a strong association with country-specific gastric cancer incidence. The CPI correlation supports the chronic inflammation carcinogenesis model, and may explain the geographic variation. We report a novel cytokine profile in Honduras that mirrors Asian populations and explains the high incidence rates. This may have dyspepsia management and screening implications for the growing US Latino population.
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