Mutations in the hepatitis C virus core gene are associated with advanced liver disease and hepatocellular carcinoma.
OBJECTIVE
Hepatitis C virus (HCV) infection can promote the development of hepatocellular carcinoma (HCC). Published data implicate the HCV core gene in oncogenesis. We tested the hypothesis that core gene sequences from HCC patients differ from those of patients without cirrhosis/HCC.


METHODS
Full-length HCV sequences from HCC patients and controls were obtained from the investigators and GenBank and compared with each other. A logistic regression model was developed to predict the HCC risk of individual point mutations and other sequence features. Mutations in partial sequences (bases 36-288) from HCC patients and controls were also analyzed. The first base of the AUG start codon was designated position 1.


RESULTS
A logistic regression model developed through analysis of full-length core gene sequences identified seven polymorphisms significantly associated with increased HCC risk (36G/C, 209A, 271U/C, 309A/C, 435A/C, 481A, and 546A/C) and an interaction term (for 209A-271U/C) that had an odds ratio <1.0. Three of these polymorphisms could be analyzed in the partial sequences. Two of them, 36G/C and 209A, were again associated with increased HCC risk, but 271U/C was not. The odds ratio of 209A-271U/C was not significant.


CONCLUSIONS
HCV core genes from patients with and without HCC differ at several positions. Of interest, 209A has been associated with IFN resistance and HCC in previous studies. Our findings suggest that HCV core gene sequence data might provide useful information about HCC risk. Prospective investigation is needed to establish the temporal relationship between appearance of the viral mutations and development of HCC.
Fishman
Sarah L
SL
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Factor
Stephanie H
SH
Balestrieri
Cinzia
C
Fan
Xiaofeng
X
Dibisceglie
Adrian M
AM
Desai
Suresh M
SM
Benson
Gary
G
Branch
Andrea D
AD
D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism
D014758:Viral Core Proteins