title: Helicobacter pylori Eradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis.
abstract: OBJECTIVE
  Helicobacter pyloriinfection induces aberrant DNA methylation in gastric mucosa. We evaluated the long-term effect ofH. pylorieradication on promotor CpG island hypermethylation in gastric carcinogenesis.
  
  
  METHODS
  H. pylori-positive patients with gastric adenoma or early gastric cancer who underwent endoscopic resection were enrolled. According toH. pylorieradication after endoscopic resection, the participants were randomly assigned toH. pylorieradication or non-eradication group.H. pylori-negative gastric mucosa from normal participants provided the normal control. CpG island hypermethylation of tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and median values of hypermethylation were compared after one year byH. pyloristatus.
  
  
  RESULTS
  InH. pylori-positive patients, hypermethylation of p16 was found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In theH. pylorieradication group, methylation rates of p16 and CDH1 decreased in 58.1% and 61.3% of the patients, and the median values of hypermethylation were significantly lower at one year compared with the non-eradication group. However, RUNX-3 hypermethylation did not differ significantly at one year afterH. pylorieradication. The non-eradication group hypermethylation did not change after one year.
  
  
  CONCLUSIONS
  H. pyloriinfection was associated with promotor hypermethylation of genes in gastric carcinogenesis, andH. pylorieradication might reverse p16 and CDH1 hypermethylation.
authors.affiliation: Department of Internal Medicine, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sang Gyun
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Byeong Gwan
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Koh
authors.affiliation: Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors.forename: Kook Lae
authors.initials: KL
authors.lastname: Lee
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000209:etiology*
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D050677:Core Binding Factor Alpha 3 Subunit; D019941:Cyclin-Dependent Kinase Inhibitor p16; C493729:Runx3 protein, human
keywords: CDH1; Carcinogenesis; CpG hypermethylation; Helicobacter pylori; p16