Relationships between p16 gene promoter methylation and clinicopathologic features of colorectal cancer: a meta-analysis of 27 cohort studies.

Many existing studies have demonstrated that p16 promoter methylation might be correlated with the clinicopathologic features of colorectal cancer (CRC), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationships between p16 promoter methylation and the clinicopathologic features of CRC. We searched the CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through August 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under fixed- or random-effects models. Twenty-seven clinical cohort studies were included with a total of 3311 CRC patients. Our meta-analysis results revealed that p16 promoter methylation was associated with pathological characteristics of CRC (tumor, nodes, metastasis stage: OR=1.55, 95% CI: 1.14-2.13, p=0.006; lymph node metastasis: OR=2.40, 95% CI: 1.37-4.19, p=0.002; histologic grade: OR=2.72, 95% CI: 1.63-4.54, p<0.001; Dukes stage: OR=2.06, 95% CI: 1.57-2.71, p=0.002; tumor size: OR=1.99, 95% CI: 1.03-3.85, p=0.041; location: OR=2.49, 95% CI: 1.95-3.18, p<0.001, respectively). Subgroup analysis by ethnicity suggested that there were also significant correlations between p16 gene promoter methylation and pathological characteristics of CRC among both Caucasian and Asian populations (all p<0.05). Our meta-analysis suggests that promoter methylation of the p16 gene may be strongly correlated with the clinicopathologic features of CRC. Thus, p16 gene promoter methylation may be a potential biomarker for CRC.