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Meta-Analysis
. 2013 Sep 26;8(9):e72633.
doi: 10.1371/journal.pone.0072633. eCollection 2013.

Association between MGMT promoter methylation and non-small cell lung cancer: a meta-analysis

Affiliations
Meta-Analysis

Association between MGMT promoter methylation and non-small cell lung cancer: a meta-analysis

Changmei Gu et al. PLoS One. .

Abstract

Background: O(6)-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.

Methods: We 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.

Results: A 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.

Conclusion: This 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow diagram of the stepwise selection from associated studies.
Figure 2
Figure 2. Forest plot of MGMT methylation in tumor tissue verse control group between MGMT promoter methylation and NSCLC.
Figure 3
Figure 3. Sensitivity analysis by omitting a single study at a time on the overall effect.
Figure 4
Figure 4. Funnel plot for assessment of publication bias.
Each hollow point represents a separate study for the indicated association. The area of the hollow point reflects the weight (inverse of the variance). Horizontal line stands for the mean magnitude of the effect.

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