A pro-inflammatory genotype predisposes to Barrett's esophagus

Carcinogenesis. 2008 May;29(5):926-31. doi: 10.1093/carcin/bgm241. Epub 2008 Jan 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Barrett Esophagus / genetics*
  • Cytokines / genetics*
  • Endoscopy
  • Female
  • Genotype
  • Hernia, Hiatal / genetics
  • Humans
  • Inflammation / genetics*
  • Interleukin-10 / genetics
  • Interleukin-12 / genetics
  • Interleukin-2 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • Male
  • Middle Aged
  • Mucous Membrane / physiopathology
  • Polymorphism, Genetic
  • White People

Substances

  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Interleukin-8
  • Interleukin-10
  • Interleukin-12