title: Alterations of Cyclooxygenase-2 Methylation Levels Before and After Intervention Trial to Prevent Gastric Cancer in a Chinese Population.
abstract: To explore the epigenetic mechanisms underlying the effects of anti-Helicobacter pylori (H. pylori) alone and combined with COX-2 inhibitor (celecoxib), we dynamically evaluated the associations between COX-2 methylation alterations and gastric lesion evolution during the process of interventions. In a total of 809 trial participants COX-2 methylation levels were quantitatively detected before and after treatment. The self-comparison at the same stomach site for each subject showed significant methylation alteration differences among intervention groups (P < 0.001). With placebo group as reference, COX-2 methylation levels were decreased in anti-H. pylori [OR, 3.30; 95% confidence interval (CI), 2.16-5.02], celecoxib (OR, 2.04; 95% CI, 1.36-3.07), and anti-H. pylori followed by celecoxib (OR, 2.10; 95% CI, 1.38-3.17) groups. When stratified by baseline histology, the three active arms significantly decreased COX-2 methylation levels in indefinite dysplasia/dysplasia subjects, and ORs were 3.65 (95% CI, 1.96-6.80) for anti-H. pylori, 2.43 (95% CI 1.34-4.39) for celecoxib, and 2.80 (95% CI, 1.52-5.15) for anti-H. pylori followed by celecoxib, respectively. No additive effect on COX-2 methylation was found for anti-H. pylori followed by celecoxib than two treatments alone. Compared with subjects without methylation reduction, higher opportunity for gastric lesion regression was found in subjects with decreased COX-2 methylation levels, especially for indefinite dysplasia/dysplasia subjects (OR, 1.92; 95% CI, 1.03-3.60). These findings suggest that anti-H. pylori or celecoxib treatment alone could decrease COX-2 methylation levels in gastric mucosa. COX-2 methylation alteration was associated with the regression of indefinite dysplasia/dysplasia, which might serve as a potential biomarker for chemoprevention efficacy. Cancer Prev Res; 9(6); 484-90. ©2016 AACR.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Nie
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Ma
authors.affiliation: Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China. pankaifeng2002@yahoo.com weichengyou@yahoo.com.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China. Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China. pankaifeng2002@yahoo.com weichengyou@yahoo.com.
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D000068579:Celecoxib / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib