Aberrant Methylation of MGMT Promoter in HNSCC: A Meta-Analysis

Abstract

BackgroundO6-methylguanine-DNA methyl-transferase (MGMT) gene, a DNA repair gene, plays a critical role in the repair of alkylated DNA adducts that form following exposure to genotoxic agents. MGMT is generally expressed in various tumors, and its function is frequently lost because of hypermethylation in the promoter. The promoter methylation of MGMT has been extensively investigated in head and neck squamous cell carcinoma (HNSCC). However, the association between the promoter methylation of MGMT and HNSCC risk remains inconclusive and inconsistent. Therefore, we performed a meta-analysis to better clarify the association between the promoter methylation of MGMT and HNSCC risk.MethodsA systematical search was conducted in PubMed, Web of Science, EMBASE, and Ovid for studies on the association between MGMT promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (CI) were calculated to estimate association between MGMT promoter methylation and risk of HNSCC. The meta-regression and subgroup analysis were undertaken to explore the potential sources of heterogeneity.ResultsTwenty studies with 1,030 cases and 775 controls were finally included in this study. The frequency of MGMT promoter methylation was 46.70% in HNSCC group and 23.23% in the control group. The frequency of MGMT promoter methylation in HNSCC group was significantly higher than the control group (OR = 2.83, 95%CI = 2.25–3.56).ConclusionThis meta-analysis indicates that aberrant methylation of MGMT promoter was significantly associated with the risk of HNSCC, and it may be a potential molecular marker for monitoring the disease and may provide new insights to the treatment of HNSCC.

Association between MGMT Promoter Methylation and Risk of Breast and Gynecologic Cancers: A Systematic Review and Meta-Analysis

“…In addition, it has been reported that MGMT gene expression in normal and neoplatic tissues varies and MGMT promoter methylation was associated with better suvivial in some cancer types but not all 47 . In the present study, we showed that MGMT promoter methylation status was significantly associated with an increased risk of breast and gynecologic cancers, which is consistent with previous studies in head and neck squamous cell carcinoma, lung cancer, glioblastoma, and esophageal cancer 9 – 11 . These works including ours highlighted the possibility of using MGMT promoter methylation status as a biomarker 49 , based on the facts that MGMT promoter hypermethylation could occur early in the neoplastic process before the clinical manifestation 29 , 50 , 51 , or turn up in normal appearing tissues close to tumors 52 , 53 .…”

“…The hypermethylation of CpG islands is relatively rare in normal cells, thus the detection of methylated DNA in bodily fluids can be promising 8 . Several studies have focused on this in other cancers including head and neck squamous cell carcinoma, lung cancer and esophageal cancer 9 – 11 . Nevertheless, for breast and gynecologic cancers, although many studies have explored the association between their risks and MGMT promoter hypermethylation, the results remain inconsistent 12 – 39 .…”

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

“…MGMT encodes an adduct repair enzyme of O 6 -methylguanine generated by the interaction of DNA with alkylating agents present, for example, in cigarette smoke (Christmann and Kaina, 2012). The MGMT promoter methylation can reduce the protein expression having therefore oncogenic potential (Cai et al, 2016). Although our report is not the first to point out the prognostic value of MGMT for HNSCC patients, there is no consensus among studies previously published.…”

Epigenetic Modifications in Head and Neck Cancer

“…The gene MGMT (O6-methylguanine-DNA methyltransferase) is related to DNA repair, and increased methylation in its promoter has been reported in HNSCC (Koutsimpelas et al 2012;Chaisaingmongkol et al 2012;Dvojakovska et al 2018). In a meta-analysis based on 20 studies, the promoter of MGMT was hypermethylated in HNSCC compared to healthy controls, suggesting a connection between higher methylation and an increased risk of head and neck cancer (Cai et al 2016). Metaanalysis of OSCC cases also confirmed higher methylation in this promoter (Don et al 2014) and in addition, the increased methylation was connected with a lower level of MGMT protein (Koutsimpelas et al 2012).…”