Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma.
Recently, hepatitis B virus (HBV) genotypes and mutations have been reported to be related to hepatocellular carcinoma (HCC). This cross-sectional case-control study examined the relationship between HCC and mutations in the enhancer II/core promoter and precore regions of HBV by comparing 135 Korean HCC patients infected with HBV genotype C2 (HBV/C2; HCC group) with 135 age-, sex-, and hepatitis B e antigen (HBeAg) status-matched patients without HCC (non- HCC group). Age and sex were also matched between HBeAg-positive and -negative patients. The prevalence of T1653, A1689, V1753, T1762/A1764, T1846, A1850, C1858, and A1896 mutations was evaluated in this population. The prevalence of the T1653 mutation in the box alpha region, the T1689 [corrected] mutation in between the box alpha and beta regions, and the T1762/A1764 mutations in the basal core promoter region was significantly higher in the HCC group compared to the non-HCC group (8.9% vs. 2.2%, P = 0.017; 19.3% vs. 4.4%, P < 0.001; and 60.7% vs. 22.2%; P < 0.001). Among HBeAg-negative patients, the frequency of the T1653 mutation was higher in the HCC group. Regardless of HBeAg status, the prevalence of the T1689, [corrected] and T1762/A1764 mutations was higher in the HCC group than in the non-HCC group. However, no association was observed between mutations in the precore region and HCC. Upon multivariate analysis, the presence of the T1653, T1689, [corrected] and T1762/A1764 mutations was an independent predictive factor for HCC. The addition of the T1653 or T1689 [corrected] mutation to T1762/A1764 increased the risk of HCC. In conclusion, the T1653, T1689, [corrected] and/or T1762/A1764 mutations were associated with the development of HCC in Korean patients infected with HBV/C2.
Kim
Ja Kyung
JK
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Chang
Hye Young
HY
Lee
Jung Min
JM
Baatarkhuu
Oidov
O
Yoon
Young Joon
YJ
Park
Jun Yong
JY
Kim
Do Young
DY
Han
Kwang-Hyub
KH
Chon
Chae Yoon
CY
Ahn
Sang Hoon
SH
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein