Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation.

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.

• Authors: A O O Chan, J Z Peng, S K Lam, K C Lai, M F Yuen, H K L Cheung, Y L Kwong, A Rashid, C K Chan, B C-Y Wong
• Journal: Gut (Gut) Vol. 55 Issue 4 Pg. 463-8 (Apr 2006) ISSN: 0017-5749 [Print] England
• PMID: 16428266 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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