Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer

Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobocter pylori neutrophil activating [HP-NAP] protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, we have aimed to assess the risk of gastritis and gastric cancer in the co-presence of these two inflammation modulating mediators

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Methods: Gastritis [n=58] and gastric cancer [n=31] patients were evaluated and compared with H. py/or/-positive asymptomatic controls [n=46], for serum antibodies against recombinant HP-NAP and IL-4 C-590T single nucleotide polymorphism using immunoblotting and PCR-RFLP, respectively. Multivariable logistic regression, adjusting for age, gender and ethnicity, was used for data analysis

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Results: In terms of susceptibility to gastritis, seropositivity to HP-NAP projected a risk impact of 4.62 fold [OR=4.62, 95% Cl=l.50-14.22], which when present in IL-4 -590 T carriers augmented the risk up to 9.7 fold [OR=9.70, 95% CI=2.06-45.69]

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A similar pattern, but of a stronger magnitude, occurred for the risk of gastric cancer, which was estimated at 9.07 fold [OR=9.07, 95% Cl=1.99-42.0] for HP-NAP-seropositive subjects and was drastically amplified [OR=33.64, 95% 0=2.06-548.68], when double-positive [HP-NAP seropositive/IL-4 -590 T carrier] subjects were examined against double negatives [HP-NAP seronegative/IL-4 -590 CC]

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Conclusion: Our preliminary data indicate that serum antibodies against HP-NAP represent a state of risk, which is further exacerbated in IL-4 -590 T carriers. These biomarkers, if validated in larger prospective studies, can be used to screen for gastric cancer susceptibility