P16 gene hypermethylation and hepatocellular carcinoma： A systematic review and meta-analysis

AIM： To quantitatively investigate the effect of p16 hypermethylation on hepatocellular carcinoma （HCC） and hepatocirrhosis using a meta-analysis of available casecontrol studies. METHODS： Previous studies have primarily evaluated the incidence of p16 hypermethylation in HCC and corresponding control groups, and compared the incidence of p16 hypermethylation in tumor tissues, pericancer liver tissues, normal liver tissues and non-tumor liver tissues with that in other diseases. Data regarding publication information, study characteristics, and incidence of p16 hypermethylation in both groups were collected from these studies and summarized. RESULTS： Fifteen studies, including 744 cases of HCC and 645 non-tumor cases, were identified for metaanalysis. Statistically significant odds ratios （ORs） of p16 hypermethylation were obtained from tumor tis- sues and non-tumorous liver tissues of HCC patients （OR 7.04, 95% CI： 3.87%-12.78%, P 〈 0.0001）, tu- mor tissues of HCC patients and healthy liver tissues of patients with other diseases （OR 12.17, 95% CI： 6.64%-22.31%, P 〈 0.0001）, tumor tissues of HCC pa- tients and liver tissues of patients with non-tumorous liver diseases （OR 6.82, 95% CI： 4.31%-10.79%, P 〈 0.0001）, and cirrhotic liver tissues and non-cirrhotic liver tissues （OR 4.96, 95% CI： 1.45%-16.96%, P = 0.01）. The pooled analysis showed significantly in- creased ORs of p16 hypermethylation （OR 6.98, 95% CI： 4.64%-10.49%, P 〈 0.001） from HCC tissues and cirrhotic tissues. CONCLUSION： P16 hypermethylation induces the inactivation of p16 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC and liver cirrhosis.