title: Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk.
abstract: Specific sequence changes in codons 70 and 91 of the hepatitis C virus genotype 1b (HCV GT1b) core gene have been associated with increased risk of hepatocellular carcinoma (HCC). Essentially all previous studies were conducted in Asian populations with a wide range of liver disease, and none were conducted specifically in GT1a-infected individuals. We conducted a pilot study in a multiethnic population in the USA with HCV-related cirrhosis to determine if this association extended to GT1a-infected individuals and to determine if other sequence changes in the HCV core gene were associated with HCC risk. HCV core gene sequences from sera of 90 GT1 HCV carriers with cirrhosis (42 with HCC) were analysed using standard RT-PCR-based procedures. Nucleotide sequence data were compared with reference sequences available from GenBank. The frequency of sequence changes in codon 91 was not statistically different between HCC (7/19) and non-HCC (11/22) GT1b carriers. In GT1a carriers, sequence changes in codon 91 were observed less often than in GT1b carriers but were not observed in non-HCC subjects (4/23 vs 0/26, P = 0.03, Fisher's exact test). Sequence changes in codon 70 were not distributed differently between HCC and non-HCC GT1a and 1b carriers. Most importantly, for GT1a carriers, a panel of specific nucleotide changes in other codons was collectively present in all subjects with HCC, but not in any of the non-HCC patients. The utility of this test panel for early detection of HCC in GT1a-infected individuals needs to be assessed in larger populations, including longitudinal studies.
authors: Department of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.|Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
authors: Brent
authors: B
authors: Korba
authors: Division of Gastroenterology & Hepatology, Johns Hopkins University, Sibley Memorial Hospital, Washington, DC 20016, USA.
authors: Kirti
authors: K
authors: Shetty
authors: Department of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.
authors: Alexei
authors: A
authors: Medvedev
authors: Department of Microbiology and Immunology, Georgetown University, Washington, DC 20057, USA.
authors: Prasanth
authors: P
authors: Viswanathan
authors: Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Rency
authors: R
authors: Varghese
authors: Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Bin
authors: B
authors: Zhou
authors: Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Rabindra
authors: R
authors: Roy
authors: Department of Biostatistics, Georgetown University, Washington, DC 20057, USA.
authors: Kepher
authors: K
authors: Makambi
authors: Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Habtom
authors: H
authors: Ressom
authors: Department of Biostatistics, Georgetown University, Washington, DC 20057, USA.|Department of Oncology, Georgetown University, Washington, DC 20057, USA.
authors: Christopher A
authors: CA
authors: Loffredo
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D003062:Codon; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012307:Risk Factors
chemical_list: D003062:Codon; D006512:Hepatitis B Core Antigens