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 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.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.

Risk factors for combined hepatocellular-cholangiocarcinoma:A hospital-based case-control study

AIM:To identify risk factors contributing to the development of combined hepatocellular-cholangiocarcinoma(CHC) in China.METHODS:One hundred and twenty-six patients with CHC and 4:1 matched healthy controls were interviewed during the period from February 2000 to October 2012.Logistic regression analysis was used to calculate odds ratios(OR)and 95%confidence intervals(CI)for each risk factor.RESULTS:Univariate analysis showed that the significant risk factors for CHC development were hepatitis B virus(HBV)infection,heavy alcohol consumption,a family history of liver cancer,and diabetes mellitus.Multivariate stepwise logistic regression analysis showed that HBV infection(OR=19.245,95%CI:13.260-27.931)and heavy alcohol consumption(OR=2.186,95%CI:1.070-4.466)were independent factors contributing to the development of CHC.CONCLUSION:HBV infection and heavy alcohol consumption may play a role in the development of CHC in China.