Promoter hypermethylation of MGMT gene may contribute to the pathogenesis of gastric cancer: A PRISMA-compliant meta-analysis.

Beckground: The association of MGMT (O-methyguanine deoxyribonucleic acid methyltransferase) promoter hypermethylation with gastric cancer (GC) risk has been studied extensively, but the results remained unclear. Here, we performed a meta-analysis to evaluate whether promoter hypermethylation of the MGMT gene contributed to gastric pathogenesis.

Methods: Relevant studies were identified by retrieving the PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases. The Newcastle-Ottawa Scale was applied to assess methodological quality of the included studies. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the association of MGMT promoter hypermethylation with gastric pathogenesis. Moreover, STATA 12.0 software was used to summarize the extracted data in this meta-analysis.

Results: Seventeen studies, comprising 1736 cases and 1291 controls, were included in this meta-analysis. The frequency of MGMT promoter hypermethylation in the GC group (32.97%) was significantly higher than those in the control group (18.00%) (OR = 2.83, CI = 1.93-4.15, P < .05). When stratified by cancer subtype, the results indicated that the frequency of MGMT promoter hypermethylation was significantly higher in gastric adenocarcinoma than in control group (OR = 3.47, CI = 1.06-11.35, P < .05). In addition, MGMT promoter hypermethylation significantly promoted distant metastasis and lymph node (LN) metastasis of gastric tumor (for distant metastasis, OR = 4.22, CI = 2.42-7.37, P < .05; for LN metastasis, OR = 1.56, CI = 1.14-2.13, P < .05). A significant association between MGMT promoter hypermethylation and TNM-stage was also found in the present meta-analysis (OR = 2.70, CI = 1.79-4.08, P < .05).

Conclusion: The results of this meta-analysis suggested that MGMT gene-promoter hypermethylation was significantly associated with an increased risk of GC, especially in Asians. Furthermore, MGMT gene-promoter hypermethylation might be correlated with the distant metastasis and LN metastasis of GC.