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

Tumor necrosis factor-alpha （TNF-a） is an important cytokine in generating an immune response against infection with hepatitis C virus （HCV）. The functions of TNF-a may be altered by single-nucleotide polymorphisms （SNPs） in its gene structure. We hypothesized that SNPs in TNF-a 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-a 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-a 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-a -308 position, the G/G allele was most common （78.5%） in the study population, with the G/A and NA 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-a were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-a -308 polymorphism does not influence the production of TNF-a. The serum level of TNF-a was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-a -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.