title: Role of P14 and MGMT gene methylation in hepatocellular carcinomas: a meta-analysis.
abstract: BACKGROUND
  This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC).
  
  
  METHODS
  We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC.
  
  
  RESULTS
  Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues.
  
  
  CONCLUSIONS
  These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.
authors.affiliation: Department of Public Health, Qingdao University Medical College, Qingdao, China E-mail : jinziling1201@163.com.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Li
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Yu
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Cui
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Piao
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C401561:CDK2AP2 protein, human; D015513:Oncogene Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes