Hepatitis B Virus Whole Genome Variants and Hepatocellular Carcinoma Risk: Nested Case-Control Study
Date Issued
2008
Date
2008
Author(s)
Lan, Pei-Wen
Abstract
Background & Aims：Development of hepatocellular carcinoma (HCC) may be associated with complex variants in full-length genome of HBV. The aim of this study was to identify the genetic variants that might affect the progression from healthy HBV carrier state to HCC.aterials and Methods：Baseline plasma samples were collected from 120 cases and 128 controls nested within a cohort of male HBV carriers. Phylogenetic analysis was performed with complete genome of HBV to determine the genotypes and subtypes. We used logistic regression and risk-score analysis to identify single-nucleotide polymorphisms (SNPs) signature to predict HCC.esults：Of the 161 subjects infected with genotype B HBV, 90.1% were infected with subtype Ba, 5.6% with Ba/Bj, and 4.3% with a new subtype. Of the 76 subjects infected with genotype C HBV, 82.9% were infected with subtype Ce, 11.8% with Ce/Cs, and 5.3% with Cs. For genotype B HBV, subtype was associated with HBeAg/anti-HBe status, the presence of T1858 or A1896 variants, and viral load. For genotype C, subtype was associated with the presence of T1858 or A1896 variants but not other viral factors. Among the 1815 nucleotide positions with SNPs in the complete genome of HBV, we identified 291 associated with HCC. One hundred sixty-six of the above SNPs were also correlated with viral load, 82 of which reside in the P gene. These P gene SNPs majorly cluster in the three enzymatic domains. Using logistic regression and risk score analysis, we identified a 5-SNP signature combined with known HBV-related factors for the prediction of HCC in the training set. This 5-SNP signature was validated by the testing set.onclusions：In natural situation, SNPs that might affect viral load cluster in the P gene region. We identified a 5-SNP signature associated with HCC after taking account of other known viral factors.
Subjects
Hepatitis B virus
Hepatocellular carcinoma
phylogenetic analysis
subtype
nucleotide variants
model
SDGs
Type
thesis
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