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Journal of Clinical Microbiology, October 2007, p. 3191-3197, Vol. 45, No. 10
0095-1137/07/$08.00+0 doi:10.1128/JCM.00411-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Influence of Hepatitis B Virus X and Core Promoter Mutations on Hepatocellular Carcinoma among Patients Infected with Subgenotype C2
Noboru Shinkai,1,2
Yasuhito Tanaka,1
Kiyoaki Ito,2
Motokazu Mukaide,1,3
Izumi Hasegawa,4
Yasuhiro Asahina,5
Namiki Izumi,5
Hiroshi Yatsuhashi,6
Etsuro Orito,2
Takashi Joh,2 and
Masashi Mizokami1*
Departments of Clinical Molecular Informative Medicine,1 Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601,2 SRL Inc., 51 Komiya, Hachiouji, Tokyo 192-8535,3 Department of Gastroenterology, Chukyo Hospital, Nagoya 457-8510,4 Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo 180-8610,5 Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Oomura, Nagasaki 856-8562, Japan6
Received 22 February 2007/ Returned for modification 30 April 2007/ Accepted 23 June 2007
Hepatitis B virus (HBV) genotypes/subgenotypes and their related mutations in the HBV genome have been reported to be associated with hepatocellular carcinoma (HCC). To determine the HCC-associated mutations of the HBV genome in the entire X, core promoter, and precore/core regions, a cross-sectional control study was conducted comparing 80 Japanese patients infected with HBV C2 and suffering from HCC with 80 age-, sex-, and hepatitis B e antigen (HBeAg) status-matched patients without HCC (non-HCC group). Each HBeAg-positive group (31 with HCC; 29 without HCC) and HBeAg-negative group (49 with HCC; 51 without HCC) was also matched with respect to age and sex. The C1479, T1485, H1499, A1613, T1653, V1753, T1762/A1764, and A1896 mutations were frequent in this population. The prevalences of the T1653 mutation in the box 
region and the V1753 and T1762/A1764 mutations in the basal core promoter region were significantly higher in the HCC group than in the non-HCC group (56% versus 30%, 50% versus 24%, and 91% versus 73% [P = 0.0013, P = 0.0010, and P = 0.0035, respectively]). The platelet count was significantly lower for the HCC group than for the non-HCC group (10.7 x 104 ± 5.1 x 104 versus 17.3 x 104 ± 5.1 x 104 platelets/mm3 [P < 0.0001]). Regardless of HBeAg status, the prevalence of the T1653 mutation was higher in the HCC group (52% versus 24% [P = 0.036] for HBeAg-positive patients and 59% versus 33% [P = 0.029] for HBeAg-negative patients). In the multivariate analysis, the presence of T1653, the presence of V1753, and a platelet count of 
10 x 104/mm3 were independent predictive factors for HCC (odds ratios [95% confidence intervals], 4.37 [1.53 to 12.48], 7.98 [2.54 to 25.10], and 24.39 [8.11 to 73.33], respectively). Regardless of HBeAg status, the T1653 mutation increases the risk of HCC in Japanese patients with HBV/C2.
* Corresponding author. Mailing address: Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan. Phone: 81-52-853-8292. Fax: 81-52-842-0021. E-mail: mizokami{at}med.nagoya-cu.ac.jp
Published ahead of print on 25 July 2007.
Journal of Clinical Microbiology, October 2007, p. 3191-3197, Vol. 45, No. 10
0095-1137/07/$08.00+0 doi:10.1128/JCM.00411-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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