Tumor necrosis factor-alpha -308G/A polymorphism and risk of hepatocellular carcinoma in hepatitis C virus-infected patients

Chin J Cancer. 2012 Jan;31(1):29-35. doi: 10.5732/cjc.011.10258. Epub 2011 Dec 23.


Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5%) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1%, respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94%, 4%, and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha