title: Role of p16 gene promoter methylation in gastric carcinogenesis: a meta-analysis.
abstract: This meta-analysis was performed to evaluate the relationships between promoter DNA methylation in tumor suppressor gene p16 and gastric carcinogenesis. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library and CBM databases were searched for relevant articles published before November 1st, 2013 without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated. Forty-seven clinical cohort studies that met all inclusion criteria were included in this meta-analysis. A total of 2,813 gastric cancer (GC) patients were assessed. Our meta-analysis results revealed that the frequencies of p16 promoter methylation in the GC tissues were higher than those of normal and adjacent tissues (Normal: OR = 23.04, 95% CI = 13.55-39.15, P < 0.001; Adjacent: OR = 4.42, 95% CI = 1.66-11.76, P = 0.003; respectively). Furthermore, we observed significant associations of p16 promoter methylation with TNM stage, histologic grade, invasive grade, lymph node metastasis of GC (TNM stage: OR = 3.60, 95% CI: 2.17-5.98, P < 0.001; Histologic grade: OR = 2.63, 95% CI: 1.55-4.45, P < 0.001; Invasive grade: OR = 3.44, 95% CI: 1.68-7.06, P = 0.001; Lymph node metastasis: OR = 2.68, 95% CI: 1.66-4.32, P < 0.001; respectively). However, there were no correlations of p16 promoter methylation with the TNM stage and Helicobacter pylori (HP) infection of GC (Tumor size: OR = 0.76, 95% CI: 0.14-4.07, P = 0.746; HP infection: OR = 1.31, 95% CI: 0.75-2.27, P = 0.342; respectively). Our findings provide empirical evidence that p16 promoter methylation may play an important role in gastric carcinogenesis. Thus, p16 promoter methylation may be a promising potential biomarker for the early diagnosis of GC.
authors.affiliation: Department of General Surgery, The Shengjing Hospital of China Medical University, Huaxiang Road, Tiexi District, Shenyang, 110022, People's Republic of China, wangheling1127@126.com.
authors.forename: He-Ling
authors.initials: HL
authors.lastname: Wang
authors.forename: Ping-Yi
authors.initials: PY
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D044466:Asian People; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D042241:Early Diagnosis; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16