title: Methylation status of blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.
abstract: BACKGROUND
  To evaluate the relationship between methylation status of blood leukocyte DNA and risk of gastric cancer, a population-based study was conducted in Linqu County.
  
  
  METHODS
  Methylation levels of IGFII and N33 were determined by quantitative methylation-specific PCR. The temporal trend of methylation levels during gastric cancer development was investigated in 133 gastric cancer cases from two cohorts with pre- and/or post-gastric cancer samples. As the references of pre-GCs, 204 intestinal metaplasia (IM) or dysplasia (DYS) subjects who did not progress to gastric cancer during the follow-up period were selected. Meanwhile, 285 subjects with superficial gastritis/chronic atrophic gastritis (SG/CAG) were also selected as controls.
  
  
  RESULTS
  IGFII median methylation level was significantly higher in gastric cancer cases than those with SG/CAG (61.47% vs. 49.73%; P < 0.001). IGFII and N33 methylation levels were elevated at least 5 years ahead of clinical gastric cancer diagnosis comparing with SG/CAG (63.38% vs. 49.73% for IGFII, 9.12% vs. 5.70% for N33; all P < 0.001). Furthermore, the frequency of hypermethylated IGFII was markedly increased in IM or DYS subjects who progressed to gastric cancer in contrast to those who remained with IM and DYS, and adjusted ORs were 12.52 [95% confidence interval (CI), 3.81-41.15] for IM and 10.12 (95% CI, 2.68-38.22) for DYS. Similar results were also found for N33 in subjects with IM (OR, 3.77; 95% CI, 1.20-11.86).
  
  
  CONCLUSIONS
  Our findings suggested that hypermethylated IGFII and N33 in blood leukocyte DNA were associated with risk of gastric cancer in a Chinese population.
  
  
  CONCLUSIONS
  IGFII and N33 methylation status may be related to gastric carcinogenesis.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Su
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China. weichengyou@yahoo.com pankaifeng2002@yahoo.com.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.affiliation: Healthy Bureau of Linqu County, Shandong, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Liu
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Molecular Oncology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Yuasa
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China. weichengyou@yahoo.com pankaifeng2002@yahoo.com.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C035170:IGF2 protein, human; D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins; D007335:Insulin-Like Growth Factor II