Abstract
Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis.
Highlights
Viral genomic mutations may contribute to hepatocellular carcinoma (HCC) development
We assumed that basal core promoter (BCP) A1762T/G1764A dual mutations might promote hepatocarcinogenesis even without progression to cirrhosis
The most common naturally occurring mutations in the BCP A1762T/G1764A dual mutation has been associated with hepatocarcinogenesis, but conflicts still exist [1,3]
Summary
Viral genomic mutations may contribute to HCC development. HBV nonstructural X protein (HBx) is a key regulatory protein of the virus and is at the intersection of HBV infection, replication, pathogenesis, and possibly carcinogenesis. HBx has different consequences for hepatocyte physiology because HBV-infected cells are targeted by the immune system or as hepatocytes, in which HBx is expressed, and undergo transformation and progression to HCC. The roles that HBx mutations play in hepatocarcinogenesis remain controversial, for the basal core promoter (BCP) A1762T/G1764A dual mutation. Several prospective studies have demonstrated that patients with an A1762T/G1764A dual mutation were more predisposed to HCC than those with the wild type and that HBV mutations, including A1762T/ G1764A, are associated with an increased risk of HCC [2]. A recent study using global data found no significant difference in BCP mutations between HCC and non-HCC patients with HBV genotype C, and the differences between chronic hepatitis B (CHB) and liver cirrhosis (LC) and between LC and HCC were not www.impactjournals.com/oncotarget significant, the mutant ratio increased with disease progression. A recent study using global data found no significant difference in BCP mutations between HCC and non-HCC patients with HBV genotype C, and the differences between chronic hepatitis B (CHB) and liver cirrhosis (LC) and between LC and HCC were not www.impactjournals.com/oncotarget significant, the mutant ratio increased with disease progression. [3]
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