DNMT3A −448A>G polymorphism and the risk for hepatocellular carcinoma

Abstract

DNA-methyltransferase (DNMT) 3A plays a significant role in carcinogenesis. Findings of a previous study suggested an association between the DNMT3A -448A>G single-nucleotide polymorphism (SNP) and susceptibility to gastric cancer (GC) and colorectal cancer (CRC). Hepatocellular carcinoma (HCC) is a common malignancy, with a similar expression pattern to GC. The aim of this case-control study was to determine whether there is an association between DNMT3A gene polymorphism and susceptibility to HCC. Real-time quantitive PCR (qPCR) was employed to detect DNMT3A expression in tumor and non-cancer liver tissue from 13 HCC patients. An increased expression of DNMT3A was detected, as well as -448A>G polymorphisms of DNMT3A promoter by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP), confirmed by sequencing. The distribution of -448A>G polymorphisms was examined in 108 HCC patients and 225 healthy controls who were matched for age and gender. The association of -448A>G polymorphisms of DNMT3A and the risk of HCC was evaluated by stratified analysis according to the patient's age and gender. The allele frequency of -448A among HCC patients and the controls was 24.07 vs. 24.22%, respectively. The frequency of genotypes GG, AG, AA was 55.56 vs. 56.89%, 40.74 vs. 37.78%, 3.7 vs. 5.33%, respectively. The results indicated that -448A>G is not associated with susceptibility to HCC, although -448A>G is a functional single-nucleotide polymorphism (SNP) and increased the expression of DNMT3A in HCC cases. Findings of the present study suggested that the DNMT3A -448A>G polymorphism is an insufficient biomarker to predict the susceptibility to HCC.