title: Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.
abstract: OBJECTIVE
  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.affiliation: Department of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Dominguez
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.forename: Paris E
authors.initials: PE
authors.lastname: Heidt
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Martin
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Galanko
authors.forename: Oluwaseun A
authors.initials: OA
authors.lastname: Omofoye
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000208:ethnology* / Q000235:genetics; D016480:Helicobacter pylori; D006721:Honduras / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D013274:Stomach Neoplasms / Q000150:complications / Q000208:ethnology* / Q000235:genetics*
chemical_list: D016207:Cytokines