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- Title
A pro-inflammatory genotype predisposes to Barretts esophagus.
- Authors
L.M.G. Moons; J.G. Kusters; J.H.M. van Delft; E.J. Kuipers; R. Gottschalk; H. Geldof; W.A. Bode; J. Stoof; A.H.M. van Vliet; H.B. Ketelslegers; J.C.S. Kleinjans; P.D. Siersema
- Abstract
Introduction: Severity of mucosal inflammation is shown to be associated with Barretts 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 (A흟), IL-10 (Câ592A, Câ819T, Aâ1082G), IL-8 (Aâ251T), IL-6 (Gâ174C) and IL-2 (Gâ330T) 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) 1.2â2.7; Pâ=â0.007). 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 1.32â6.58; Pâ=â0.008). The IL-10â1082 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 1.05â1.85; Pâ=â0.011). 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.
- Subjects
GENETIC research; GENETIC polymorphisms; INFLAMMATION; CYTOKINES
- Publication
Carcinogenesis, 2008, Vol 29, Issue 5, p926
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgm241