A pro-inflammatory genotype predisposes to Barrett's esophagus

L.M. Moons, J.G. Kusters, J.H. van Delft, E.J. Kuipers, R. Gottschalk, H. Geldof, W.A. Bode, J. Stoof, A.H. van Vliet, H.B. Ketelslegers, J.C. Kleinjans, P.D. Siersema

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    Abstract

    INTRODUCTION: Severity of mucosal inflammation is shown to be associated with Barrett's esophagus (BE) development in animals. It has therefore been postulated that a strong pro-inflammatory host response predisposes to BE. AIM: To determine the impact of cytokine gene polymorphisms on the development of BE. METHODS: The multiplex SNaPshot method was used to determine interleukin (IL)-12B (A+1188C), IL-10 (C-592A, C-819T, A-1082G), IL-8 (A-251T), IL-6 (G-174C) and IL-2 (G-330T) gene polymorphisms in 255 patients with BE and 247 patients with reflux esophagitis (RE). RESULTS: The presence of the IL-12B C-allele, which is associated with increased IL-12p70 expression, was more frequently observed in BE than in RE patients [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.2-2.7; P = 0.007). The risk of BE was increased in patients in whom the IL-12B C-allele coincided with a hiatal hernia (OR 2.9; 95% CI 1.32-6.58; P = 0.008). The IL-10(-1082) GG genotype, which is associated with higher IL-10 levels, was also associated with a decreased risk of BE when it was associated with the IL-12B C-allele, indicating IL-10-dependent down-regulation of IL-12p70 expression. A combination of the IL-12B AA genotype and the IL-10 AA or AG genotypes was associated with RE (OR 1.4; 95% CI 1.05-1.85; P = 0.011). CONCLUSION: A genetic profile predisposing to a strong pro-inflammatory host response, mediated by IL-12p70 and partially dependent on IL-10, is associated with BE. This risk further increases when this genotype coincides with a hiatal hernia, suggesting that exposure to gastroesophageal reflux in the presence of a pro-inflammatory genetic background is a driving force in the development of BE.
    Original languageEnglish
    Pages (from-to)926-31
    JournalCarcinogenesis
    Volume29
    Issue number5
    DOIs
    Publication statusPublished - 1 Jan 2008

    Cite this

    Moons, L. M., Kusters, J. G., van Delft, J. H., Kuipers, E. J., Gottschalk, R., Geldof, H., Bode, W. A., Stoof, J., van Vliet, A. H., Ketelslegers, H. B., Kleinjans, J. C., & Siersema, P. D. (2008). A pro-inflammatory genotype predisposes to Barrett's esophagus. Carcinogenesis, 29(5), 926-31. https://doi.org/10.1093/carcin/bgm241