title: Tumor necrosis factor-alpha 308.2 polymorphism is associated with advanced hepatic fibrosis and higher risk for hepatocellular carcinoma.
abstract: OBJECTIVE
  Host genetic factor and hepatic fibrosis may predispose to risk for hepatocellular carcinoma (HCC). This study aimed to assess the association between tumor necrosis factor (TNF) alpha polymorphism and hepatic fibrosis, and risk for HCC.
  
  
  METHODS
  One hundred eight pairs of gender-matched and age-matched patients with HCC and unrelated healthy controls were genotyped for TNF308.2 and TNF238.2 alleles with polymerase chain reaction and direct sequencing.
  
  
  RESULTS
  The frequency of TNF308.1/TNF308.2 genotype in cases was higher than that in controls [odds ratio (OR) = 4.37]. Multivariate analysis indicated that TNF308.2 allele (OR = 3.23), hepatitis B surface antigen (OR = 17.17), and antibodies to hepatitis C virus (OR = 45.52) were independent risk factors for HCC. Surrogate markers for significant fibrosis implied that cases with the TNF308.2 allele have more advanced liver fibrosis. Moreover, multivariate analysis indicated that cirrhosis with Child-Pugh grade C, low serum albumin, and low platelet count were independent risk factors for carrying the TNF308.2 allele.
  
  
  CONCLUSIONS
  TNF308.2 allele carriage and chronic hepatitis B virus/hepatitis C virus infection are independent risk factors for HCC. Carriage of the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to a higher risk for HCC.
authors.affiliation: Department of Clinical Laboratory, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jen-Eing
authors.initials: JE
authors.lastname: Jeng
authors.forename: Jung-Fa
authors.initials: JF
authors.lastname: Tsai
authors.forename: Lee-Yea
authors.initials: LY
authors.lastname: Chuang
authors.forename: Mei-Shang
authors.initials: MS
authors.lastname: Ho
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Min-Yuh
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Shin-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: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha