title: 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.
abstract: To assess the contribution of tumor necrosis factor (TNF)β +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. TNFβ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that TNFβ 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 TNFβ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with TNFβ 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 α-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with TNFβ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that TNFβ 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 TNFβ 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.
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan E-mail : jftsai@cc.kmu.edu.tw.
authors.forename: Jen-Eing
authors.initials: JE
authors.lastname: Jeng
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Wu
authors.forename: Meng-Feng
authors.initials: MF
authors.lastname: Tsai
authors.forename: Huey-Ru
authors.initials: HR
authors.lastname: Tsai
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Min-Yuh
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Shinn-Chern
authors.initials: SC
authors.lastname: Chen
authors.forename: Wan-Lung
authors.initials: WL
authors.lastname: Chuang
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Jung-Fa
authors.initials: JF
authors.lastname: Tsai
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000276:immunology; D006508:Hepatitis Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D013921:Thrombocytopenia / Q000209:etiology / Q000235:genetics; D000509:alpha-Fetoproteins
chemical_list: D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D008233:Lymphotoxin-alpha; D000509:alpha-Fetoproteins