title: Methylation status of COX-2 in blood leukocyte DNA and risk of gastric cancer in a high-risk Chinese population.
abstract: BACKGROUND
  Methylation is a common epigenetic modification which may play a crucial role in cancer development. To investigate the association between methylation of COX-2 in blood leukocyte DNA and risk of gastric cancer (GC), a nested case-control study was conducted in Linqu County, Shandong Province, a high risk area of GC in China.
  
  
  METHODS
  Association between blood leukocyte DNA methylation of COX-2 and risk of GC was investigated in 133 GCs and 285 superficial gastritis (SG)/ chronic atrophic gastritis (CAG). The temporal trend of COX-2 methylation level during GC development was further explored in 74 pre-GC and 95 post-GC samples (including 31 cases with both pre- and post-GC samples). In addition, the association of DNA methylation and risk of progression to GC was evaluated in 74 pre-GC samples and their relevant intestinal metaplasia (IM)/dysplasia (DYS) controls. Methylation level was determined by quantitative methylation-specific PCR (QMSP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis.
  
  
  RESULTS
  The medians of COX-2 methylation levels were 2.3% and 2.2% in GC cases and controls, respectively. No significant association was found between COX-2 methylation and risk of GC (OR, 1.15; 95% CI: 0.70-1.88). However, the temporal trend analysis showed that COX-2 methylation levels were elevated at 1-4 years ahead of clinical GC diagnosis compared with the year of GC diagnosis (3.0% vs. 2.2%, p=0.01). Further validation in 31 GCs with both pre- and post-GC samples indicated that COX-2 methylation levels were significantly decreased at the year of GC diagnosis compared with pre-GC samples (1.5% vs. 2.5%, p=0.02). No significant association between COX-2 methylation and risk of progression to GC was found in subjects with IM (OR, 0.50; 95% CI: 0.18-1.42) or DYS (OR, 0.70; 95% CI: 0.23-2.18). Additionally, we found that elder people had increased risk of COX-2 hypermethylation (OR, 1.55; 95% CI: 1.02-2.36) and subjects who ever infected with H. pylori had decreased risk of COX-2 hypermethylation (OR, 0.54; 95% CI: 0.34-0.88).
  
  
  CONCLUSIONS
  COX-2 methylation exists in blood leukocyte DNA but at a low level. COX-2 methylation levels in blood leukocyte DNA may change during GC development.
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. susubjmu@163.com.
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Su
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. yzhang76@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. zhanglianmail@qq.com.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. 13806491812@139.com.
authors.forename: Jun-ling
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. jiyouli@126.com.
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. pan-kf@263.net.
authors.forename: Kai-feng
authors.initials: KF
authors.lastname: Pan
authors.affiliation: Key Laboratory of Carcinogenesis and Translation Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, P.R. China. weichengyou@yahoo.com.
authors.forename: Wei-cheng
authors.initials: WC
authors.lastname: You
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004247:DNA; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007962:Leukocytes; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics*
chemical_list: D004247:DNA; D051546:Cyclooxygenase 2