Tumor Necrosis Factor-Alpha Gene Polymorphism Associated With Development of Hepatitis B Virus–associated Hepatocellular Carcinoma. Issue 8 (September 2015)

• Record Type: Journal Article
• Authors: Jin, Young-Joo; Lee, Danbi; Chung, Young-Hwa; Kim, Jeong A.; Kim, Sung Eun; Lee, Yoon-Seon; Shin, Eun-Soon; Ryu, Soo Hyung; Jang, Myoung Kuk; Lee, Jong-Eun; Park, Neung Hwa
• Is Part Of: Journal of clinical gastroenterology. Volume 49:Issue 8(2015)
• Publication Date: 2015-09
• Subjects: hepatocellular carcinoma -- liver cirrhosis -- tumor necrosis factor-alpha -- genetic polymorphism -- hepatitis B virus; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Digestive organs -- Diseases; Gastroenterology; Periodicals; Periodicals; 616.33005
• DOI: 10.1097/MCG.0000000000000261
• Languages: English
• ISSNs: 0192-0790

Abstract

Abstract : Goal and Background: 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). Study: 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. Results: 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 with TNF-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). Conclusion: Our data suggest that TNF-α-857 T allele is closely associated with development of HCC in HBV-associated LC patients.