Association between P16INK4a promoter methylation and HNSCC: a meta-analysis of 21 published studies.

BACKGROUND:The p16INK4a is an important tumor suppressor gene (TSG) and aberrant methylation of promoter is known to be a major inactivation mechanism of the tumor suppressor and tumor-related genes. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of head and neck squamous cell carcinoma (HNSCC). However, some studies have reported differences in the methylation frequencies of P16INK4a promoter between cancer and the corresponding control group. Therefore, we conducted a meta-analysis to better identify the association. METHODS:PubMed, Ovid, ISI Web of Science, and EMBASE were searched to identify eligible studies to evaluate the association of p16INK4a promoter methylation and HNSCC. Odds ratio (ORs) and 95% confidence intervals (95%CI) were calculated to evaluate the strength of association between p16INK4a promoter methylation and HNSCC. RESULTS:A total of twenty-one studies with 1155 cases and 1017 controls were included in the meta-analysis. The frequencies of p16INK4a promoter methylation in the cancer group were significantly higher than those in the control group (cancer group: median: 46.67%, range = 7.84%-95.12%; control group: median: 18.37%, range = 0-83.33%; respectively). The pooled odds ratio was 3.37 (95%CI = 2.32-4.90) in the cancer group versus the corresponding control group under the random-effects model. CONCLUSION:This meta-analysis of 21 published studies identified that aberrant methylation of p16INK4a promoter was found to be significantly associated with HNSCC

Sensitivity analysis of pooled OR for <i>p16^INK4a</i> methylation and HNSCC under the random-effects model.

<p>Sensitivity analysis of pooled OR for <i>p16^INK4a</i> methylation and HNSCC under the random-effects model.</p

Characteristics of studies included in the study characteristics of included studies.

<p>M: <i>p16</i>^<i>INK4a</i> promoter methylated; U: <i>p16</i>^<i>INK4a</i> promoter unmethylated</p><p>#: A: Autologous (the control from the HNSCC themselves); H: Heterogeneous (the control from other individuals, including blood, serum, saliva or tissue).</p><p>Characteristics of studies included in the study characteristics of included studies.</p

Selection of studies in the meta-analysis.

<p>Selection of studies in the meta-analysis.</p

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

<div><p>Background</p><p>O⁶-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 <i>MGMT</i> promoter methylation and NSCLC using a meta-analysis method.</p> <p>Methods</p><p>We systematically reviewed studies of <i>MGMT</i> promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web of Science, Elsevier and CNKI databases and quantified the association between <i>MGMT</i> 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.</p> <p>Results</p><p>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 <i>MGMT</i> 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.</p> <p>Conclusion</p><p>This meta-analysis identified a strong association between methylation of <i>MGMT</i> gene and NSCLC. Prospective studies should be required to confirm the results in the future.</p> </div

The Begg’s funnel plot for assessment of publication bias in the meta-analysis.

<p>The Begg’s funnel plot for assessment of publication bias in the meta-analysis.</p

Mixed-effects model of Meta-regression analysis.

<p>Mixed-effects model of Meta-regression analysis.</p

Subgroup analysis of the association between <i>p16^INK4a</i> promoter methylation and HNSCC.

<p>†: the fixed-effects model</p><p>‡: the random-effects model</p><p>$: non-tissue: serum, saliva and blood</p><p>Subgroup analysis of the association between <i>p16^INK4a</i> promoter methylation and HNSCC.</p

Summary estimates for <i>p16^INK4a</i> promoter methylation frequency associated with HNSCC by meta-analysis.

<p>Summary estimates for <i>p16^INK4a</i> promoter methylation frequency associated with HNSCC by meta-analysis.</p