Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study

Int J Cancer. 2009 Jan 15;124(2):434-9. doi: 10.1002/ijc.23891.


To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 920 subjects with precancerous gastric lesions. H. pylori status was determined by 13C-urea breath test and the density of H. pylori in biopsy specimens used for detecting methylation status was assessed by the modified Giemsa stain. The frequency of p16 methylation was significantly higher in subjects with H. pylori positive than those with H. pylori negative in each category of gastric lesion (p<0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) of p16 methylation were markedly elevated in subjects with H. pylori positive for superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94-30.41), chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60-33.36), intestinal metaplasia (OR, 4.46; 95%CI: 2.44-8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90-7.10), and dysplasia (OR, 2.48; 95%CI: 1.02-5.99). Moreover, the frequencies of p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02-16.13 times higher in subjects with mild H. pylori infection, and 2.69-38.73 times higher in those with moderate/severe infection, respectively. Our findings indicate that p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • China
  • CpG Islands
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • DNA Methylation
  • Female
  • Gastric Mucosa / microbiology*
  • Gastritis / microbiology*
  • Genes, p16*
  • Helicobacter Infections / complications*
  • Helicobacter pylori / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Precancerous Conditions
  • Promoter Regions, Genetic*
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / microbiology*


  • Cyclin-Dependent Kinase Inhibitor p16