Study On The Relationship Between The Mutations Of Hepatitis B Virus X Gene And Precore Gene, Related Factors And Hepatocellular Carcinoma

Objective:To understand HBV X gene, C gene mutations of patients with HBV relatedhepatocellular carcinoma (HCC) and chronic hepatitis B (CHB). So as to furtherstudy the relationship between position of HBV variants and the factors associatedand HCC, which can provide ideas for clinical prevention of HBV associated HCC.Methods:To collected the morning fasting serum and clinical data of43patients withHBV associated hepatocellular carcinoma (liver cancer group) and54patients withchronic hepatitis B (Chronic hepatitis B group) in the Shanxi Medical University firsthospital outpatient or hospitalization in2011July─2012August. And then to detectvirology indexes, HBVDNA level, and to analyze the mutations, using PCR productdirect sequencing method for detection of hepatitis B virus X and Precore genesequence. To analyse the relationship between HCC occurrence and age, gender,HBVDNA level, HBeAg status, HBV X gene and C gene mutations in two groups byusing the method of case-control. Data entry and statistical analysis use SPSSl3.0software. Measurement data use t test, Comparison of the rate use χ2test or Fishers’sexact probability. Single factor analysis of groups use independent samples t test,inspection level a=0.05, and P<0.05has statistical significance.Results:There were41effective cases in liver cancer group and54effective cases inchronic hepatitis B group. 1. The results of the analyses of the clinical data of the two groups of patients（1）The age of HCC patients(58.00±9.58years) was higher than that of CHBpatients(40.78±10.04years),and the difference was statistically significant（t=8.442,P=0.000）；（2）The ratio of male to female was30/11in patients with HCC,and the ratiowas33/21in patients with HCC. There was no significant difference in sex ratio ofHCC patients and CHB patients2（χ=1.517,P=0.218）；（3）The HBeAg-negative rate of HCC patients was68.29%（28/41）and it washigher than that of CHB patients which was33.33%（18/54）,and the difference wasstatistically significant in the two group2（χ=11.404,P=0.001）；（4）The HBV DNA level of HCC patients was4.67±0.91log10copies/ml and itwas lower than that of CHB patients which was5.60±1.27log10copies/ml,and thedifference was statistically significant in the two group（t=-4.169,P=0.000）.2.There were no significant difference in the mutation rates of HBV X generegion’s G1440A, G1467C, G/C1479T/A、C1485T、C1653T and HBV Precoregene region’s G1896A of the HCC patients and CHB patients (P>0.05).3.The mutation rates of HBV X gene region’s T1674C、T1753C、A1762T/G1764A and HBV Precore gene region’s G1896A were statisticallysignificant (P <0.05) between the HCC patients and CHB patients, and the mutationrate of HCC patients was higher than that of CHB patients.4.The mutation rates of T1753C, A1762T/G1764A and G1896A in HBeAgnegative patients were higher those in the HBeAg-positive patients，and the differencewere statistically significant (P <0.05), but the mutation rates of T1674C were nosignificant difference between the HBeAg negative patients and the HBeAg-positivepatients (P>0.05). 5.The HBV DNA levels of A1762T/G1764A mutation group was lower than thatof the unmutated group，and the difference were statisticallysignificant(t=-2.406,P=0.016),but there were no significant difference betweenT1674C, T1753C, and G1896A mutation groups and the unmutated groups (P>0.05).6.The ages of T1674C,A1762T/G1764A,G1896A3point mutations groups werehigher than those of the non-mutated groups, and the difference were statisticallysignificant (P <0.05), but those of the T1753C mutation group and the unmutatedgroup were no significant difference (P>0.05).7.The rat of insertion or deletion mutations of HBV DNA X gene and Precoregene are lower than the point mutatios between the HCC patients and CHB patients.Conclusion:1. The mutations of HBV X gene region’s T1674C, T1753C, A1762T/G1764Aand HBV Precore gene region’s G1896A were closely related with the occurrence ofhepatocellular carcinoma.2. Rate of insertion or deletion HBV DNA X gene and Precore gene are lowerthan point mutations in the serum. The mutations of HBV X gene region’s T1753C,A1762T/G1764A, and Precore gene region’s G1896A can inhibit the expression ofHBeAg,but the mutation of T1674C did not affect the expression of HBeAg.3. With the growth of the age, the risk of mutations of HBV X gene region’sT1674C,T1753C,A1762T/G1764A,and Precore gene region’s G1896A may increase.But mutation of T1753C was not influenced by age.The mutation of A1762T/G1764Amay inhibit replication of HBV DNA. But the mutations of T1674C, T1753C andG1896A has no obvious influence on replication of HBV DNA.4. The study found that HBV X gene region’s T1674C mutation rate of thepatients with HCC was higher than that of chronic HBV infection. In addition, the study found that this gene region’s C1485T and C1653T mutations were not closelyassociated with the occurrence of HCC, which was different from the relevant reports.This may be related to patients living environment and other factors,and further studyneeds to be done.