Associations of MGMT promoter hypermethylation with squamous intraepithelial lesion and cervical carcinoma: A meta-analysis

Abstract

BackgroundIn this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC.MethodsLiterature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes.ResultsIn this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79–4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer.ConclusionThe meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer.

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

“…appears also in other human cancers such as cervical cancer [167], lung cancer [168], and glioblastoma [169].…”

“…Meta-analysis of 10 studies comprising 910 ovarian tissue samples by Qiao et al concluded that the inactivation of MGMT might be associated with carcinogenesis in specific histological types of EOC [26]. Aberrant MGMT promoter methylation appears also in other human cancers such as cervical cancer [167], lung cancer [168], and glioblastoma [169].…”

MGMT Methylation Is Associated with Human Papillomavirus Infection in Cervical Dysplasia: A Longitudinal Study

“…Previous studies have investigated this variable in multiple cancer types including colon cancer [34][35][36][37][38][39][40], neck squamous cell carcinoma [41,42], ovarian cancer [43], and breast cancer [44]. Certain studies have found that the abnormal methylation of MGMT was strongly associated with the risk and histological type of cervical cancer [24,45].…”

“…Studies have shown a tendency for the accumulation of DNA methylation, an important epigenetic mechanism for gene silencing, to be associated with disease severity, and this has been supported by findings in cervical premalignancy and malignancy [20,23]. Research has also revealed that a key factor in DNA repair is O6-methylguanine-DNA methyltransferase (MGMT), the function of which involves removing mutagenic and cytotoxic adducts from O6-guanine in DNA [24,25]. Specifically, alkyl adducts are removed from the O6 position of guanine in DNA by MGMT, leading to the development of resistance against alkylating agents.…”