Gastric cancer and the high combination prevalence of host cytokine genotypes and Helicobacter pylori in Honduras.
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.
Morgan
Douglas R
DR
Department of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Dominguez
Ricardo L
RL
Keku
Temitope O
TO
Heidt
Paris E
PE
Martin
Christopher F
CF
Galanko
Joseph A
JA
Omofoye
Oluwaseun A
OA
Sandler
Robert S
RS
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*
D016207:Cytokines