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J Clin Gastroenterol. 2015 Sep;49(8):e76-81. doi: 10.1097/MCG.0000000000000261.

Tumor Necrosis Factor-Alpha Gene Polymorphism Associated With Development of Hepatitis B Virus-associated Hepatocellular Carcinoma.

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*Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon †Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center ‡DNAlink Ltd ∥Department of Internal Medicine, University of Inje College of Medicine, Seoul Paik Hospital ¶Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul §Department of Internal Medicine, Hallym University College of Medicine, Pyeongchon Sacred Heart Hospital, Pyeongchon #Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.



Host genetic diversity may play roles in development of HCC. This study was conducted to validate the effects of tumor necrosis factor-alpha (TNF-α) gene polymorphism on development of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV).


The study cohort comprised 224 patients with HBV-associated HCC and 206 with HBV-associated liver cirrhosis (LC). Using chromosomal DNA, TNF-α promoter gene polymorphisms were determined at 3 common single-nucleotide polymorphism (SNP) sites (TNF-α-1031 T>C, TNF-α-857 C>T, and TNF-α-308 G>A) using a single base extension method. The genotype distributions were compared between the 2 groups. All the HBV-associated LC patients were followed up regularly every 6 to 12 months for surveillance of HCC development.


In the cross-sectional analysis, the frequency of TNF-α-857 T allele was much higher in patients with HCC compared with those with LC (42% vs. 31%, P<0.01). Of 206 HBV-associated LC patients, 12 (5.8%) developed HCC during the median follow-up period of 36 months. The cumulative occurrence rates of HCC were significantly higher in patients with TNF-α-857 T allele than those withTNF-α-857 C/C genotype (1-, 3-, and 5-y rates: 2.9%, 12.8%, and 20.7% vs. 0%, 3.1%, and 5.3%, respectively; P=0.013). However, the other genetic polymorphisms of TNF-α promoter gene did not affect the development of HCC. In multivariate analysis, TNF-α-857 T allele was a significant predictor of HCC development (hazard ratio 6.29, P=0.01).


Our data suggest that TNF-α-857 T allele is closely associated with development of HCC in HBV-associated LC patients.

[Indexed for MEDLINE]

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