Association between MGMT Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

Abstract

BackgroundO6-methylguanine-DNA methyltransferase (MGMT) is one of most important DNA repair enzyme against common carcinogens such as alkylate and tobacco. Aberrant promoter methylation of the gene is frequently observed in non-small cell lung cancer (NSCLC). However, the importance of epigenetic inactivation of the gene in NSCLC published in the literature showed inconsistence. We quantified the association between MGMT promoter methylation and NSCLC using a meta-analysis method.MethodsWe systematically reviewed studies of MGMT promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web of Science, Elsevier and CNKI databases and quantified the association between MGMT promoter methylation and NSCLC using meta-analysis method. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to evaluate the strength of association. Potential sources of heterogeneity were assessed by subgroup analysis and meta-regression.ResultsA total of 18 studies from 2001 to 2011, with 1, 160 tumor tissues and 970 controls, were involved in the meta-analysis. The frequencies of MGMT promote methylation ranged from 1.5% to 70.0% (median, 26.1%) in NSCLC tissue and 0.0% to 55.0% (median, 2.4%) in non-cancerous control, respectively. The summary of OR was 4.43 (95% CI: 2.85, 6.89) in the random-effects model. With stratification by potential source of heterogeneity, the OR was 20.45 (95% CI: 5.83, 71.73) in heterogeneous control subgroup, while it was 4.16 (95% CI: 3.02, 5.72) in the autologous control subgroup. The OR was 5.31 (95% CI: 3.00, 9.41) in MSP subgroup and 3.06 (95% CI: 1.75, 5.33) in Q-MSP subgroup.ConclusionThis meta-analysis identified a strong association between methylation of MGMT gene and NSCLC. Prospective studies should be required to confirm the results in the future.

DNA methylation: its role in transcriptional regulation and association with lung cancer

“…72 Furthermore, in order to empower the precision of the diagnostic outcome of each study, several meta-analyses have been conducted. 70,[73][74][75] Taking into account the results of many individual studies, these meta-analyses confirmed that the methylation status of MGMT, 70 CDKN2A, 74 APC, 75 and RARβ 73 promoters is strongly related to lung cancer development.…”

P16INK4a gene promoter methylation as a biomarker for the diagnosis of non‐small cell lung cancer: An updated meta‐analysis

“…Promoter methylation of tumor suppressor genes is common in body fluid and can be used as a lung cancer diagnosis method or biomarker. Several studies have evaluated its clinical application with acceptable diagnostic performance and high specificity …”

“…Promoter methylation of tumor suppressor genes is frequently detected in cancer tissue and body fluid in malignant carcinomas such as lung, colorectal, and esophageal cancers. Previous studies have reported that methylation of the P16 INK4a gene promoter is common in lung cancer.…”

5-Azacytidine enhances efficacy of multiple chemotherapy drugs in AML and lung cancer with modulation of CpG methylation

“…Besides, we observed a greater overlap of genes in AML and NSCLC that are associated with significantly hypomethylated CG sites and that might indicate the existance of several target genes. Some of these genes include candidate tumor suppressor genes like MGMT (37,38), THRB (39,40), L3MBTL4 (41), EDNRB (42), CDH13 (43) and TGFBR3 (44).…”