title: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong.
authors.forename: A O O
authors.initials: AO
authors.lastname: Chan
authors.forename: J Z
authors.initials: JZ
authors.lastname: Peng
authors.forename: S K
authors.initials: SK
authors.lastname: Lam
authors.forename: K C
authors.initials: KC
authors.lastname: Lai
authors.forename: M F
authors.initials: MF
authors.lastname: Yuen
authors.forename: H K L
authors.initials: HK
authors.lastname: Cheung
authors.forename: Y L
authors.initials: YL
authors.lastname: Kwong
authors.forename: A
authors.initials: A
authors.lastname: Rashid
authors.forename: C K
authors.initials: CK
authors.lastname: Chan
authors.forename: B C-Y
authors.initials: BC
authors.lastname: Wong
mesh_terms: D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D017291:Clarithromycin / Q000627:therapeutic use; D019175:DNA Methylation; D004359:Drug Therapy, Combination; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007422:Intestines / Q000473:pathology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D015820:Cadherins; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole