Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation

Gut. 2006 Apr;55(4):463-8. doi: 10.1136/gut.2005.077776. Epub 2006 Jan 20.

Abstract

Background: E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients.

Aim: To examine if eradication of H pylori could reverse E-cadherin methylation.

Methods: Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing.

Results: Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5).

Conclusion: H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Ulcer Agents / therapeutic use
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Chronic Disease
  • Clarithromycin / therapeutic use
  • DNA Methylation
  • Drug Therapy, Combination
  • Female
  • Gastric Mucosa / metabolism
  • Gastritis / drug therapy
  • Gastritis / genetics*
  • Gastritis / metabolism
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / genetics*
  • Helicobacter Infections / metabolism
  • Helicobacter pylori*
  • Humans
  • Immunohistochemistry / methods
  • Intestines / pathology
  • Male
  • Metaplasia
  • Middle Aged
  • Omeprazole / therapeutic use
  • Promoter Regions, Genetic / genetics*
  • Prospective Studies

Substances

  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Cadherins
  • Amoxicillin
  • Clarithromycin
  • Omeprazole