Influence of hepatitis B virus X and core promoter mutations on hepatocellular carcinoma among patients infected with subgenotype C2.
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 alpha 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 10(4) +/- 5.1 x 10(4) versus 17.3 x 10(4) +/- 5.1 x 10(4) platelets/mm(3) [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 < or =10 x 10(4)/mm(3) 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.
Shinkai
Noboru
N
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Tanaka
Yasuhito
Y
Ito
Kiyoaki
K
Mukaide
Motokazu
M
Hasegawa
Izumi
I
Asahina
Yasuhiro
Y
Izumi
Namiki
N
Yatsuhashi
Hiroshi
H
Orito
Etsuro
E
Joh
Takashi
T
Mizokami
Masashi
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000150:complications* / Q000821:virology; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D014758:Viral Core Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein