The Association Between MGMT Promoter Methylation and Patients with Gastric Cancer: A Meta-Analysis

Genet Test Mol Biomarkers. 2017 Apr;21(4):213-221. doi: 10.1089/gtmb.2016.0284. Epub 2017 Feb 23.

Abstract

Aims: Several previous studies have suggested that MGMT promoter methylation is significantly associated with gastric cancer, but the results were not consistent. Hence, we conducted a systematic meta-analysis to explore the potential correlation of MGMT promoter methylation with gastric cancer and its clinicopathologic characteristics.

Materials and methods: Searches of PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) literature databases were conducted to identify relevant studies published in English or Chinese before July 1, 2016. The meta-analysis was performed using Stata 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between MGMT promoter methylation and gastric cancer. We also conducted a subgroup analysis and metaregression to explore sources of heterogeneity.

Results: We identified 12 articles that met the inclusion criteria. The 12 articles described 14 studies that included 1571 tumor tissues and 1243 controls. The meta-analysis results demonstrated that the frequency of MGMT promoter methylation was higher in gastric cancer tissues compared with adjacent tissues and normal tissues (OR = 4.06, 95% CI: 2.55-6.46, p < 0.001; OR = 8.85, 95% CI: 1.15-68.23, p = 0.036; respectively). An assessment of the correlation between MGMT promoter methylation and clinicopathological characteristics indicated that MGMT promoter hypermethylation was significantly associated with tumor-node-metastasis stage, lymph node metastasis, and distant metastasis (OR = 2.11, 95% CI: 1.18-3.75, p = 0.011; OR = 1.99, 95% CI: 1.47-2.68, p < 0.001; and OR = 3.60, 95% CI: 2.17-5.95, p < 0.001; respectively).

Conclusion: Our findings provide evidence that MGMT promoter methylation could play an important role in gastric carcinogenesis and may serve as an important biomarker for gastric cancer progression.

Keywords: DNA methylation; MGMT; gastric cancer.

Publication types

  • Meta-Analysis

MeSH terms

  • Asian People
  • Biomarkers, Tumor
  • Case-Control Studies
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics*
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Neoplasm Metastasis / genetics
  • Odds Ratio
  • Promoter Regions, Genetic / genetics
  • Risk Factors
  • Stomach Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes