Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach

Clin Cancer Res. 2006 May 15;12(10):3216-21. doi: 10.1158/1078-0432.CCR-05-2442.

Abstract

Purpose: Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori-infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium.

Experimental design: Endoscopic biopsies were taken from the antrum and corpus of H. pylori-infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication.

Results: Among the 28 H. pylori-infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001).

Conclusion: Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation.

MeSH terms

  • Adult
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Cadherins / metabolism*
  • Cell Transformation, Neoplastic
  • DNA Methylation*
  • Female
  • Gastric Mucosa
  • Helicobacter Infections / complications
  • Helicobacter Infections / drug therapy*
  • Helicobacter pylori
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Pyloric Antrum / chemistry
  • Stomach / microbiology
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / prevention & control

Substances

  • Cadherins