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lüll Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis Liu S; Zhang H; Gu C; Yin J; He Y; Xie J; Cao GJ Natl Cancer Inst 2009[Aug]; 101 (15): 1066-82BACKGROUND: The association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis remains controversial because of conflicting data in the literature. We conducted a meta-analysis of case-control and cohort studies to examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore mutations in relation to the risk of hepatocellular carcinoma (HCC). METHODS: We searched databases for studies of these associations that were published in English or Chinese up to August 31, 2008. HBV mutation-specific odds ratios and relative risks were pooled by use of a random-effects model and stratified by potential confounders. All statistical tests were two-sided. RESULTS: Of the 43 studies included in this meta-analysis, 40 used a case-control design. The 43 studies evaluated a total of 11 582 HBV-infected participants, of whom 2801 had HCC. Statistically significant summary odds ratios of HCC were obtained for any PreS mutation (3.77, 95% confidence interval [CI] = 2.57 to 5.52), C1653T in EnhII (2.76, 95% CI = 2.09 to 3.64), T1753V (2.35, 95% CI = 1.63 to 3.40), and A1762T/G1764A in BCP (3.79, 95% CI = 2.71 to 5.29). PreS mutations were more strongly associated with an increased risk of HCC in subjects who were infected with HBV genotype C than in those who were infected with HBV genotype B, whereas the opposite was true for A1762T/G1764A. C1653T, T1753V, and A1762T/G1764A were more strongly associated with an increased risk of HCC in hepatitis B e antigen (HBeAg)-positive subjects than in HBeAg-negative subjects. PreS mutations, C1653T, T1753V, and A1762T/G1764A accumulated during the progression of chronic HBV infection from the asymptomatic carrier state to HCC (P(trend) < .001 for each mutation). PreS mutations, C1653T, C1653T + T1753V, and A1762T/G1764A-based combinations of mutations had specificities greater than 80% for the prediction of HCC. The precore mutations G1896A and C1858T were not associated with the risk of HCC, regardless of HBeAg status and HBV genotype. CONCLUSIONS: HBV PreS mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. These mutations alone and in combination may be predictive for hepatocarcinogenesis.|*Mutation[MESH]|Carcinoma, Hepatocellular/*virology[MESH]|Case-Control Studies[MESH]|Cohort Studies[MESH]|Confounding Factors, Epidemiologic[MESH]|DNA, Viral/genetics[MESH]|Genotype[MESH]|Hepatitis B Surface Antigens/blood[MESH]|Hepatitis B virus/*genetics/immunology[MESH]|Hepatitis B, Chronic/*complications[MESH]|Hepatitis C, Chronic/complications[MESH]|Humans[MESH]|Liver Cirrhosis/complications[MESH]|Liver Neoplasms/*virology[MESH]|Odds Ratio[MESH]|Predictive Value of Tests[MESH]|Protein Precursors/*genetics[MESH]|Research Design[MESH]|Sensitivity and Specificity[MESH]|Viral Envelope Proteins/*genetics[MESH] |