B型肝炎病毒核基因序列變異與肝細胞癌之關係：重疊病例對照研究
Genetic Variation in Core gene of Hepatitis B Virus and Hepatocellular Carcinoma : A Nested Case-Control Study
Date Issued
2006
Date
2006
Author(s)
Jung, Chun-Ming
DOI
zh-TW
Abstract
Background: The association between sequence variation in the core gene of hepatitis B virus (HBV) and the development of hepatocellular carcinoma (HCC) is largely unknown. Materials and Methods: Study subjects consisted of 116 cases and 153 controls nested within a cohort study of 4841 male, asymptomatic HBV carriers enrolled from 1988 through 1992. Controls were matched to the cases with respect to age at recruitment and blood collection time. Pearson correlation coefficient and factor analysis were employed to identify cosegregating nucleotide variant. HBV genotype was determined by phylogenetic analysis with the use of the neighbor-joining method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. Results: The mean percentages of nucleotide divergence were 3.10% (95% CI= 2.50% to 3.69%) in cases and 2.87% (95% CI= 2.40% to 3.34%) in controls. High nucleotide divergence clustered in the nucleotide region 2059-2354. Of the 27 single nucleotide polymorphisms (SNPs) statistically significantly associated with HCC, 10 (at positions 2059, 2104, 2134, 2170, 2233, 2251, 2290, 2293, 2296, and 2354) were highly correlated with genotype, showing a correlation coefficient of greater than 0.6. Results from factor analysis and phylogenetic analysis suggested that the 10 SNPs could be used as the signature SNPs to detect different genotypes in Taiwanese population. In analysis based on deduced amino acid (aa) sequence, we found aa substitution at three positions aa13, aa21, and aa113 was statistically significantly associated with the risk of HCC after adjusting for HBV genotype, showing OR of 0.30 (95% CI=0.11 to 0.80), 0.22 (95% CI =0.08 to 0.58), and 0.40 (95% CI=0.19 to 0.84), respectively. Based the combinations of 12 SNPs with poor or no correlation with genotype, prototype accounts for 47.4% of the HBV genomes isolated from cases and 24.2% of the HBV genomes isolated from controls. HBV carriers with non-prototype were at reduced risk (adjusted OR=0.43, 95% CI=0.24 to 0.77) of HCC compared with those who had the prototype. Conclusions: Nucleotide sequence variation in HBV core gene was majorly located at epitopes of T or B cell. Amino acid substitution in the core gene was significantly associated with the development of HCC.
Subjects
B型肝癌病毒
肝細胞癌
核基因
核甘酸
HBV
HCC
core gene
nucleotide
SDGs
Type
thesis
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