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

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. pylon status was determined by C-13-urea breath test and the density of H. pylon 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. pylon positive than those with H. pylori negative in each category or gastric lesion (p < 0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) 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 or p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylon 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. (C) 2008 Wiley-Liss. Inc.