HBV infection is associated with p14 (ARF) , p15 (INK4B) , p16 (INK4A) , and RB gene methylation (P = 0.048, 0.035, 0.02); HBV-DNA replication is associated with p14 (ARF) , p15 (INK4B) , p16 (INK4A) , and RB gene methylation (P = 0.048, 0.035, 0.02); high rate of p14 (ARF) , p15 (INK4B) , and p16 (INK4A) in HCC with HBV infection suggests that HBV-induced hypermethylation may be one of the mechanisms of HBV involved in hepatocellular carcinogenesis.
The methylation frequencies of the ten genes examined in HCC were 40.0% for p14 ( ARF ), 60.9% for p15 ( INK4b ), 70.4% for p16 ( INK4a ), 34.8% for p73, 70.4% for GSTP1, 64.3% for MGMT, 13.0% for hMLH1, 59.1% for RARbeta, 82.6% for SOCS-1, and 80.9% for OPCML.
The status of p14 was evaluated in 117 HCC tumoral nodules and 110 corresponding non-tumor tissues by loss of heterozygosity at the 9p21-22 region, homozygous deletions, single strand conformation polymorphism-polymerase chain reaction mutational analysis and methylation-specific polymerase chain reaction.
In Australian HCC the prevalence of p14 methylation increased with age (P = 0.03). p16 promoter methylation was observed in 12/37 (32%) and 6/24 (25%) in Australian and South African HCC, respectively.