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21 June 2017 : Laboratory Research  

Relationship Between Human mutL Homolog 1 (hMLH1) Hypermethylation and Colorectal Cancer: A Meta-Analysis

Hui-Feng Zhang123AB, You-Wang Lu2CD, Zhen-Rong Xie4EF, Kun-Hua Wang4AG*

DOI: 10.12659/MSM.895643

Med Sci Monit 2017; 23:3026-3038

Abstract

BACKGROUND: Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancers. Promoter hypermethylation of human mutL homolog 1 (hMLH1) has been implicated in a subset of colorectal cancers that show microsatellite instability (MSI), while the connection of the epigenetic inactivation of hMLH1 in colorectal cancers remains unknown. The aim of this study was to evaluate the relationship between the promoter hypermethylation of hMLH1 and colorectal cancers by performing a meta-analysis.

MATERIAL AND METHODS: Eligible studies were identified through searching PubMed, Cochrane Library, Web of Science, and Google Scholar databases. R Software including meta packages was used to calculate the pooled and odds ratios (ORs) with corresponding confidence intervals (CIs). Funnel plots were also performed to evaluate publication bias.

RESULTS: This meta-analysis obtained 45 articles, including 4096 colorectal cancer patients, and identified a significant association between hMLH1 hypermethylation and colorectal cancer risk using the fixed-effects model (OR=8.3820; 95% CI, 6.9202~10.1527; z=21.7431; P<0.0001) and random effects model pooled (OR=10.0963; 95% CI, 6.1919~16.4626; z=9.2688; P<0.0001). The significant relationship was found in subgroup analyses.

CONCLUSIONS: The results of this meta-analysis show a significant association between hMLH1 hypermethylation and colorectal cancer risk.

Keywords: Colorectal Neoplasms, Human Genome Project, Promoter Regions, Genetic

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416