Temporal relationship between hepatitis B virus enhancer II/basal core promoter sequence variation and risk of hepatocellular carcinoma
Journal
Gut
Journal Volume
57
Journal Issue
1
Pages
91-97
Date Issued
2008
Author(s)
Chou Y.-C.
Wu C.-F.
Yang S.-Y.
Lin C.-L.
Shin W.-L.
Liaw Y.-F.
Chen C.-J.
Abstract
Background and aims: To investigate the temporal relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP), and precore regions of hepatitis B virus (HBV) and the risk of hepatocellular carcinoma (HCC), we conducted a nested case-control study within a cohort of 4841 male HBV carriers who were recruited during the period 1988-1992. Methods: The HBV DNA sequence was determined in baseline blood samples taken from 132 incident cases and 204 controls. Base exchanges during follow-up in 71 cases were compared with 81 controls with samples taken during a similar length of follow-up. Results: Nine single nucleotide polymorphisms in the EnhII/BCP regions (six of which were genotype C HBV related) were associated with subsequent risk of HCC. The strength of these associations decreased as the lag time between baseline measurement and diagnosis increased over 3 years. However, an increased disease risk in subjects with BCP double variants (mostly T1762/A1764) or genotype C HBV-related variants was evident 9 years or more before diagnosis. The BCP double variants (odds ratio, 1.92 (95% confidence interval, 1.14 to 3.25)) were statistically significantly associated with HCC risk even after adjusting for alanine aminotransferase levels, antibodies against HBV e antigen, HBV genotype, HBV viral load, and other sequence variants. Longitudinal analysis indicated that the increased HCC risks for at-risk sequence variants were attributable to the persistence of these variants. Conclusions: HCC risk is associated with sequence variation in the EnhII/BCP regions of HBV, and persistence of at-risk sequence variants is critical for HCC development.
SDGs
Other Subjects
adult; article; blood sampling; cancer diagnosis; cancer patient; case control study; comparative study; confidence interval; control group; controlled study; disease duration; DNA sequence; follow up; genotype; helper virus; hepatitis B; Hepatitis B virus; human; liver cell carcinoma; longitudinal study; major clinical study; male; priority journal; promoter region; risk factor; single nucleotide polymorphism; statistical significance; Adult; Carcinoma, Hepatocellular; Case-Control Studies; Cohort Studies; Enhancer Elements (Genetics); Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Middle Aged; Promoter Regions (Genetics); Risk Factors
Type
journal article