Changes in Aberrant DNA Methylation After Helicobacter Pylori Eradication: A Long-Term Follow-Up Study

Int J Cancer. 2013 Nov;133(9):2034-42. doi: 10.1002/ijc.28219. Epub 2013 Jun 12.

Abstract

Changes of DNA methylation in gastric mucosae after eradication of Helicobacter pylori have not been clarified yet. From this background, we investigated time course of DNA methylation following H. pylori eradication in 221 successfully H. pylori eradicated subjects with endoscopic follow-up at least for 6 months, including 114 controls, 53 subjects with gastric dysplasia and 54 patients with early gastric cancer. All dysplasia and gastric cancer patients underwent endoscopic resection at the time of enrollment. The methylation levels in LOX, APC and MOS genes from noncancerous gastric mucosae using quantitative methylation-specific PCR, as well as the histologic findings of gastric mucosae, were compared before and after eradication. Average follow-up duration was 26.0 months (range: 6 to 76 months). H. pylori eradication decreased methylation levels in LOX (p-value for slope < 0.001) but not in APC. In MOS, decrease of its methylation level following H. pylori eradication was significant among controls without intestinal metaplasia (IM) (p-value for slope < 0.05); however, it was not observed among patients with IM or those with dysplasia or gastric cancer. After H. pylori eradication, methylation level in MOS persistently increased in patients with dysplasia or gastric cancer (p < 0.01). In conclusion, H. pylori eradication decreases aberrant DNA methylation with gene-specific manner. Methylation level in MOS is associated with IM and may be used as a surrogate marker for gastric cancer risk, regardless of H. pylori eradication history.

Keywords: Helicobacter pylori; gastric cancer; inflammation; methylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • DNA / analysis
  • DNA / genetics
  • DNA Methylation*
  • Female
  • Follow-Up Studies
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gastritis / etiology*
  • Gastritis / pathology
  • Helicobacter Infections / complications*
  • Helicobacter Infections / genetics
  • Helicobacter Infections / microbiology
  • Helicobacter pylori / pathogenicity
  • Humans
  • Intestines / microbiology
  • Intestines / pathology*
  • Male
  • Metaplasia / etiology*
  • Metaplasia / pathology
  • Middle Aged
  • Neoplasm Grading
  • Polymerase Chain Reaction
  • Precancerous Conditions / etiology*
  • Precancerous Conditions / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-mos / genetics
  • Scavenger Receptors, Class E / genetics
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / pathology

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Biomarkers, Tumor
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • DNA
  • Proto-Oncogene Proteins c-mos