title: P16 gene hypermethylation and hepatocellular carcinoma: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To quantitatively investigate the effect of p16 hypermethylation on hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available case-control 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 meta-analysis. Statistically significant odds ratios (ORs) of p16 hypermethylation were obtained from tumor tissues and non-tumorous liver tissues of HCC patients (OR 7.04, 95% CI: 3.87%-12.78%, P < 0.0001), tumor 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 patients 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 increased ORs of p16 hypermethylation (OR 6.98, 95% CI: 4.64%-10.49%, P < 0.001) from HCC tissues and cirrhotic tissues.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Health Statistics, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Zang
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.forename: Jin-Fang
authors.initials: JF
authors.lastname: Xu
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Qin
authors.forename: Rong-Xi
authors.initials: RX
authors.lastname: Shen
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D019942:Genes, p16; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio