| Objective: The outcome of hepatitis B virus (HBV) infection depends on the interaction between the virus,environment, and the host's immune response. The virus influence factors include HBV mutation, genotype, virus load, and HBeAg .HBV mutation is one of the important factors on the pathogenesis of HCC, the common mutation site include PreS deletion mutation, PreS1, PreS2, T1762/A1764, and A1896. Some studies reveal the relationship between HBV mutation and HCC, But the conclusion is not fully concordances. Various genetic mutations have been considered as the basic factor influencing HBV biological features. Evidence has been accumulating that certain HBV mutants may change the ability of replication of the virus, alter HBV antigen epitope which is related to either an exaggerated host immune response or evasion of the virus from immune surveillance, and lead to either resistance to antiviral agents. Thus, HBV mutation is associated with the persistent infection or the severe damage of hepatocyte. Aim of this study increase the samples of study objective, explore the carcinogenesis of HBV mutation and HCC.Method: In this study ,the case are HCC patients, control include chronic hepatitis B and ASC. We design primer using Primer Premier 5.0 software, the production of PCR is directly sequenced. Sequences of HBV were analyzed by MEGA 4.0 and Bioedit 7.0. We searched databases and citations in relevant articles to identify and rate studies that reported HBV mutation and HCC. HBV mutation-specific risk estimates were calculated from pooled data which were stratified by potential confounders. Combined mutations were analyzed by using included HBV sequences from GenBank database. Chi-square , T test and logistic regression were calculated by Stata 9.1 and SPSS 16.0. Results:1.Pres deletion mutation and point mutation:(1)We detected PreS1,and PreS2 deletion, and it's sart Condon mutation,79 of HCC mutated in the preS2, the OR is 2.16,95% CI (1.17-4.00).(2)We compared HCC and CHB group mutation, including C2857,A2875,T2931,T2940,A2946,A2950,A2951,G2962,A2964,T3026,T3051,T3054,T3060,A3063,A3066,T3026,T3054,T3060,A3066,G3069,T3116,A3120,G3186,C3191,T3216,C3222,T3225,C3246,G3264,C3267,C3268,A3291,T3320,T3324,T3350 position. The mutation comparison discovery, T2940, A2946, G2962, A2964, A3120, C3191, C3246, C3267, C3268, T3350 together 10 units place mutation has the significance.A2946, A3120, C3191, C3246, C3267 units place OR< 1, prompts has the protective function. Other 5 sites OR> 1, is possibly the potent dangerous factor.(3)HCC and CHB two group of PreS1 and the PreS2 area outset codon flaw and the sudden change analysis, the HCC group take the PreS2 outset codon flaw 13 examples, changes suddenly 36 examples, in the sudden change as ATA are most by the ATG sudden change; CHB the group PreS2 outset codon changes suddenly 6 examples, two group of PreS2 outset codon flaw and sudden change OR=15.64 [6.39, 38.28].HCC the group PreS1 outset codon flaw 4 examples, change suddenly 2 examples, CHB the group PreS1 outset codon flaw 2 examples, changes suddenly 1 example, the PreS1 outset codon flaw and sudden change OR=2.44 [0.60, 9.97]. 2. front C areas and the CP area flaw and changes suddenly (1) sudden change analysis: Before examination C area and CP area G1652, T1653, T1673, C1674, T1719, C1726, T1727, G1730, V1753, T1762, A1764, T1766, G1799, A1896, A1899 and A1913 altogether 16 units place sudden change difference.â‘ HCC and the CHB group compares, the OR> 1 position spot includes: T1653, C1674, V1753, T1762, A1764, T1766, A1896, A1899.â‘¡HCC and ASC group comparison, OR> 1 position spot: T1653, V1753, T1762, A1764, A1896, A1899; But the OR< 1 position spot includes: T1719, T1727, G1799.â‘¢CHB and ASC group comparison, OR> 1 position spot: T1653, V1753, T1762, A1764, A1896; OR< 1 position spot: T1719, T1727, G1730 and G1799. Between (2) different genotype comparison: In genotype B, HCC and CHB and ASC compare, C1726, T1727, T1762, A1764 have statistics difference; In genotype C, HCC and CHB and ASC compare, T1653, T1719, T1727, G1730, V1753, T1762, A1764, A1896, the A1899 position spot rate of mutation has statistics difference; In the HCC group, genotype B and genotype C compares, G1652, T1653, T1673, C1674, T1719, C1726, G1730, V1753, T1762, A1764, the G1799 position spot rate of mutation has statistics difference, in which genotype B is higher than genotype C the position spot: G1652, T1673, C1726, G1730, G1799, genotype C is higher than genotype B the position spot: T1653, C1674, T1719, V1753, T1762, A1764; In the CHB group, genotype B and genotype C compares, G1652, T1653, C1674, T1719, C1726, T1727, G1730, T1762, A1764, the G1799 position spot rate of mutation has statistics difference, in which genotype B the rate of mutation is higher than genotype C the position spot: G1652, T1673, C1726, T1727, G1730, G1799, genotype C is higher than genotype B the position spot: C1674, T1719, T1762, A1764, but T1653, V1753 rate of mutation non-statistics difference; ASC in group genotype B the rate of mutation is higher than genotype C the position spot: C1726, T1727, G1730, G1799, A1896, A1899, genotype C is higher than genotype B the position spot: T1719, but T1762, A1764 rate of mutation non-statistics difference. Between(3) Different HBeAg comparison: In HBeAg(+) HCC group and the CHB group comparison, T1653, V1753, T1762, A1764, A1896, the A1899 position spot rate of mutation has statistics difference; In the HBeAg(-) HCC group and the CHB group comparison, the T1653 position spot rate of mutation has statistics difference; HCC group different HBeAg condition PC/BCP/Enhâ…¡, The area gene mutation comparison, in A1896, the A1899 position spot has statistics difference; CHB group different HBeAg condition PC/BCP/Enhâ…¡The area gene mutation comparison, in T1653, T1719, C1726, T1727, G1730, V1753, T1762, A1764, A1896, the A1899 position spot has statistics difference.(4) Combined mutation comparative analysis: In HCC, CHB, the ASC three groups of rates of mutation have statistics difference , analyze the combination pattern which the multi-point mutation. In the CHB group , the wild type proportion (67.51%) of CHB and ASC group is higher than the HCC group obviously (28.85%). In the double mutation, HCC, CHB and in the ASC group is most common by T1762/A1764, accounts for 75.48% separately, 44.67% and 18.75%. HCC and CHB, ASC two group of or three group of chisqure examination, wild, the double mutation and three mutation has statistics difference.(5) single factor and multi-factor analysis:â‘ The HCC group and the CHB group comparison, uses the parallel grouping the single factor Logistic regression analysis. Screens has the significance variable: Age, Gender, HBeAg, AFP, ALT, T1653, V1753, T1762, A1764, T1766, T1727, A1896, A1899, C1674, PreS, C3222, A3063, A312, T3051, T3116, T3216, G2962.â‘¡Integrates the multi-factor Logistic regression analysis the single factor Logistic regression analysis screening variable, adopts method which returns gradually, further analysis the multi-dimensional regression variable, finally HCC and the CHB group comparison, the HCC occurrence and the age, PreS, T1762, T1766, the A1896 sudden change concerns.(6) Of 43 studies included, 40 used case-control design. These studies evaluated a total of 8779 HBV-infected participants, of whom 2720 had HCC. Significant summary ORs of HCC was obtained for PreS mutation (3.77, 95% confidence interval 2.57-5.52), T1653 (2.76, 2.09-3.64), V1753 (2.35, 1.63-3.40), and T1762/A1764 (3.79, 2.71-5.29). The summary ORs for T1653, V1753, and T1762/A1764 were higher in hepatitis B e antigen (HBeAg) positive groups than in HBeAg negative groups, higher in low-quality studies than in high-quality studies, and differed by HBV genotypes. PreS mutation, T1653, V1753, and T1762/A1764 accumulated during the progression of HBV chronic infection from asymptomatic carrier state to HCC (Ptrend<.001 for each mutation). PreS mutation, T1653+V1753, and T1762/A1764-based combinations were specific for the prediction of HCC. A1896 and T1858 were not significantly associated with HCC risk, irrespective of HBeAg status and genotypes.Conclusion: HBV PreS mutation, T1653, V1753, and T1762/A1764 are associated with an increased risk of HCC. These mutations and in combination are predictive for hepatocarcinogenesis. |
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