Association Of Hepatitis B Virus C1653T And A1762T/G1764A Mutation With Hepatocellular Carcinoma In Chronic Hepatitis B Virus Infection

Objective To explore the relationship of mutation in HBV enhancerⅡC1653T point and C promoter A1762T/G1764A double point with hepatocellular carcinoma.Methods 1.To investigate 104 cases of Chronic hepatitis B and 88 cases of HBV related HCC from January 2009 to May 2010 ,All patients come from five hospitals in NingXia Hui Autonomous Region,their serum and clinical data were collected , Nested polymerase chain reaction(nested PCR) was used to amplified target gene fragment(nt1606-2606), and then detected nucleotide sequence. The results were zanalyzed and compared with the standard sequences of Genbank by the software of ChromaS , to analyse the mutation of HBV enhancerⅡC1653T point and C promoter A1762T/G1764A double point in HCC group and CHB group.,Fluorescence quantitative polymerase chain reacton(FQ-PCR) and Enzyme-linked immunosorbent assay (ELISA)were used to detect HBV DNA and HBV serum marker quantity respectively. 2.To analyze the relationship between the mutation of HBV C1653T and A1762T/G1764A with HBV DNA and HBV serum marker .3.Multiple logistic regression were used to analyzed the risk factores associated with the development of HCC(p<0.05).Result:1. The incidences of C1653T mutation in HCC group were higher than CHB group(35.25% Vs 12.5%,P =0.00).2.The incidences of A1762T/G1764A double mutations in HCC group were higher than CHB group(67.05% Vs 49.04%,P =0.00).3.No difference was found between the quantity of HBV DNA in 44 patients with C1653T point mutation and that in 148 patients without the mutation(P >0.05);The quantity of HBV DNA in 120 patients with A1762T/G1764A double mutations was significantly higer than that in 70 patients without the double muatations(P =0.00 ).4. The incidences of C1653T mutation and A1762T/G1764A double mutations were much higer in 107 HBeAg negative patients(31.78% and 75.70% respectively) than in 85 HBeAg positive patients(10.59% and 34.12% respectively.P<0.01).5. Multiple logistic regression analysis showed the mutation of the C1653T and double mutation of A1762T/G1764A were all significantly associated with HCC(P=0.001,OR=4.686;P=0.007,OR=2.848).Conclusions:1. The HBV C1653T point mutation in HCC group was higer than CHB group . Multiple logistic regression analysis showed the mutation of the C1653T was risk factor for the development of HCC and may serve as a useful molecular marker for preticting the clinical outcomes in patients with chronic HBV infection.2. The HBV A1762T/G1764A double point mutation in HCC group was higer than CHB group . Multiple logistic regression analysis showed the mutation of the C1653T was risk factor for the development of HCC and may serve as a useful molecular marker for preticting the clinical outcomes in patients with chronic HBV infection.3. HBV The C1653T point mutation may had no influence on the replication capability of HBV, The A1762T/G1764A double points mutations might enhance the replication capability of HBV,4. The C1653T point mutation and A1762T/G1764A double mutations might inhibit the expression of HBeAg.