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Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

  • Jeng, Jen-Eing (Department of Laboratory Medicine, Kaohsiung Medical University Hospital) ;
  • Wu, Hui-Fang (Department of Pediatrics, Sinchu MaKay Memorial Hospital) ;
  • Tsai, Meng-Feng (Department of Pediatrics, Sinchu MaKay Memorial Hospital) ;
  • Tsai, Huey-Ru (Department of Internal Medicine, Madow Sin-Lau Hospital) ;
  • Chuang, Lea-Yea (Department of Biochemistry, Kaohsiung Medical University) ;
  • Lin, Zu-Yau (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Hsieh, Min-Yuh (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Chen, Shinn-Chern (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Chuang, Wan-Lung (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Wang, Liang-Yen (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Yu, Ming-Lung (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Dai, Chia-Yen (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University) ;
  • Tsai, Jung-Fa (Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University)
  • Published : 2015.01.06

Abstract

To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

Keywords

Tumor necrosis factor ${\beta}$ polymorphism;hepatocellular carcinoma;susceptibility;prognosis

Acknowledgement

Supported by : National Science Council

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