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. 2018 Apr 17:9:368.
doi: 10.3389/fphys.2018.00368. eCollection 2018.

Association Between hMLH1 Promoter Methylation and Risk of Gastric Cancer: A Meta-Analysis

Peng Ye  1 , Yu Shi  1 , Anling Li  1
Affiliations

Association Between hMLH1 Promoter Methylation and Risk of Gastric Cancer: A Meta-Analysis

Peng Ye et al. Front Physiol. .

Abstract

Background: Human mutL homolog 1 (hMLH1) is located on chromosome 3q21-23. As a classic tumor suppressor gene, many researchers have studied the association between hMLH1 promoter methylation and gastric cancer, but their conclusions were not always consistent. Therefore, we performed a meta-analysis to make a more integrated and precise estimate of the associations. Method: PubMed, EMBASE, and Cochrane Library were retrieved without language restrictions. Data were analyzed by Review Manager 5.2 and Stata 12.0 software. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the statistical associations. Result: A total of 39 studies published before January 20, 2018 were included in this study. The results indicated that the frequency of hMLH1 promoter methylation in gastric cancers was substantially higher than that in non-cancer controls (OR = 7.94, 95%CI = 4.32-14.58, P < 0.001). Furthermore, hMLH1 promoter methylation had considerable associations with lymph node metastasis, microsatellite instability (MSI), and low expression of hMLH1 protein (OR = 1.53, 95%CI = 1.04-2.26, P = 0.03; OR = 15.33, 95%CI = 9.26-25.36, P < 0.001; OR = 37.86, 95%CI = 18.03-79.50, P < 0.001, respectively). No association was found between hMLH1 promoter methylation and Lauren classification or Helicobacter pylori (HP) infection status. Conclusion: The present study provides evidence that promoter methylation of hMLH1 is a major causative event in the occurrence and development of human gastric cancer.

Keywords: MSI; gastric cancer; hMLH1; meta-analysis; methylation.

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Figures

Figure 1
Figure 1
Flow diagram of literature selection.
Figure 2
Figure 2
Forest plot concerning hMLH1 methylation and gastric cancer risk. The squares and horizontal lines represent the corresponding OR and 95% CI for each study. The area of the squares reflects the weight of each study. The diamond represents the pooled OR and 95% CI. Random-effect model was used.
Figure 3
Figure 3
Forest plot concerning hMLH1 methylation and lymph node metastasis. Fixed-effect model was used.
Figure 4
Figure 4
Forest plot concerning hMLH1 methylation and MSI. MSI, microsatellite instability. Fixed-effect model was used.
Figure 5
Figure 5
Forest plot concerning hMLH1 methylation and Lauren classification. Fixed-effect model was used.
Figure 6
Figure 6
Forest plot concerning hMLH1 methylation and Helicobacter pylori infection. HP, Helicobacter pylori. Fixed-effect model was used.
Figure 7
Figure 7
Forest plot concerning hMLH1 methylation and hMLH1 protein expression. Fixed-effect model was used.
Figure 8
Figure 8
The plot of sensitivity analysis for evaluating the association between hMLH1 methylation and gastric risk. The circle and horizontal dashed line represent the pooled OR and 95% CI after omitting the corresponding study.
Figure 9
Figure 9
Funnel plot for evaluating the association of hMLH1 methylation with gastric cancer risk. Each circle represents one specific study.
See this image and copyright information in PMC

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