Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.

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.

• Authors: Douglas R Morgan, Ricardo L Dominguez, Temitope O Keku, Paris E Heidt, Christopher F Martin, Joseph A Galanko, Oluwaseun A Omofoye, Robert S Sandler
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 4 Issue 9 Pg. 1103-11 (Sep 2006) ISSN: 1542-3565 [Print] United States
• PMID: 16820326 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines

Topics

• Adult
• Aged
• Aged, 80 and over
• Case-Control Studies
• Cytokines (genetics)
• Female
• Genotype
• Helicobacter Infections (complications, ethnology, genetics)
• Helicobacter pylori
• Honduras (epidemiology)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Prevalence
• Stomach Neoplasms (complications, ethnology, genetics)