title: 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.
  
  
  METHODS
  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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xin-Ran
authors.initials: XR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: weichengyou@yahoo.com.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China. Electronic address: pankaifeng2002@yahoo.com.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China; D015331:Cohort Studies; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D016481:Helicobacter Infections / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000453:epidemiology* / Q000473:pathology; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics
keywords: ALU; Gastric lesions; LINE-1; Methylation; Repetitive elements; Sat2