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.
Highlights
Gastric cancer, known as stomach cancer, continues to be a vital heath threat as the fifth leading cause of cancer and the third leading cause of death from carcinoma globally according to World Health Organization in 2014 (Stewart and Wild, 2014)
The results indicated that the frequency of Human mutL homolog 1 (hMLH1) promoter methylation in gastric cancers was substantially higher than that in non-cancer controls (OR = 7.94, 95% confidence interval (95%CI) = 4.32–14.58, P < 0.001)
Much evidence showed that hypermethylation of normally unmethylated CpG islands in the promoter regions of tumor suppressor genes was strongly related to carcinomas, for instance, BRCA1 promoter methylation in breast cancer (Zhang and Long, 2015), GSTP1 promoter methylation in prostate cancer (Jerónimo et al, 2001), hMLH1 methylation in gastroenteric tumors (Arai et al, 2010). hMLH1 is one of the human mismatched repair (MMR) genes, which is located on chromosome 3q21-23
Summary
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. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the statistical associations
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