Hypomethylation of repetitive elements in blood leukocyte DNA and risk of gastric lesions in a Chinese population.

ABSTRACT

BACKGROUND: To explore the association between hypomethylation of repetitive elements (LINE-1, Sat2, and ALU) in blood leukocyte DNA and risks of gastric lesions, and development of gastric cancer (GC), a population-based study was conducted in a high-risk area of GC in China. MATERIALS Methylation levels were determined by MethyLight in 902 subjects with various gastric lesions from two cohort studies at baseline and 276 subjects with long-term follow-up data. RESULTS: The frequency of LINE-1 or Sat2 hypomethylation was significantly increased in subjects with dysplasia (DYS) compared with superficial gastritis/chronic atrophic gastritis. The odds ratios (ORs) were 2.22 [95% confidence interval (CI) 1.45-3.40] for LINE-1 and 1.58 (95% CI 1.14-2.21) for Sat2. A dose-response pattern was found for the risk of DYS and LINE-1 hypomethylation (P-trend<0.001). Further stratified analysis indicated that the frequency of LINE-1 or Sat2 hypomethylation was higher in subjects with Helicobacter pylori infection. The ORs were 1.83 (95% CI 1.12-2.99) for LINE-1 and 1.44 (95% CI 1.01-2.05) for Sat2. The follow-up data indicated that the risk of progression to GC was increased in intestinal metaplasia (IM) subjects with LINE-1 hypomethylation (OR=2.82; 95% CI 1.17-6.77) or Sat2 hypomethylation (OR=2.78; 95% CI 1.15-6.74). The risk of progression to GC was also increased in DYS subjects with Sat2 hypomethylation (OR=5.24; 95% CI 2.00-13.74). CONCLUSIONS: These findings suggest that hypomethylation of repetitive elements in blood leukocytes is associated with the risks of advanced gastric lesions and development of GC.