| Autor: |
Moons, Leon, Kusters, JG (Johannes), van Delft, JHM, Kuipers, Ernst, Gottschalk, R, Geldof, H, Bode, WA, Stoof, Jeroen, van Vliet, AHM (Arnoud), Ketelslegers, HB, Kleinjans, JCS, Siersema, PD (Peter) |
| Přispěvatelé: |
Gastroenterology & Hepatology |
| Rok vydání: |
2008 |
| Zdroj: |
Carcinogenesis, 29(5), 926-931. Oxford University Press |
| ISSN: |
0143-3334 |
| Popis: |
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 (TM) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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