| Summary: | 碩士 === 國立臺灣大學 === 流行病學研究所 === 92 === Background: The aim of this study was to investigate the association between variation in the core promoter (CP) and precore (PC) regions of HBV genome and HCC. We also assessed the associations of the genetic variants of HBV with genotype and plasma DNA levels.
Methods: A nested case-control study involving a total of 124 cases and 159 controls derived from a cohort of 4841 male HBV carriers was conducted. For cases, both blood samples drawn at baseline and collected during follow-up within two years before the time of cancer diagnosis were used for analysis of viral factors. Controls were matched to cases by year of birth and the times of blood drawn. The second time-point analysis included 79 cases and 92 controls.
Results: At baseline, a total of 11 genetic variants were associated with HCC, giving adjusted ORs of from 2~5. The ORs of HCC associated with haboring 1762T/1764A double mutation and 1896G were 3.15 (95%CI=1.84-5.41) and 1.78 (95%CI=1.05-2.99), respectively. The risk of HCC increased with increacing number of genetic variants of HBV (test for trend, P<0.0001). For most of the study subjects, the HBV genetic variation was the same in the base-line samples and in the samples collected at follow-up. The OR of HCC for each genetic variant was increased among subjects persistently harboring “variant type”. Genetic variation in the PC region was not associated with HBV genotype, but variation in the CP region was more prevalent in subjects with C genotype than in those with non-C genotype. After adjusting potential confounders including age and genotype, all the genetic variants were not significantly associated with HBV viral load, except 1896G. We did not find evidence for a modification effect of genotype on the association between genetic variants in the CP/PC regions of HBV and HCC.
Conclusion: Genetic variants in the CP/PC region of HBV were associated with the development of HCC. HBV genotype was associated with variation in CP but not PC. Most variants (except 1896G) appeared not to affect the replication activity of HBV.
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