Polymorphism of the TLR4 gene reduces the risk of hepatitis C virus-induced hepatocellular carcinoma

Oncology. 2012;82(1):35-40. doi: 10.1159/000335606. Epub 2012 Jan 26.

Abstract

Objective: Toll-like receptor 4 (TLR4) signalling participates in the innate immune response against hepatitis C virus (HCV) infection. TLR4 gene polymorphisms may influence the risk of HCV-induced hepatocellular carcinoma (HCC). This is a single-centre-based study designed to analyse the distribution of several TLR4 gene single nucleotide polymorphisms in healthy controls and in patients chronically infected with HCV, with and without HCC.

Methods: We have determined three single nucleotide polymorphisms (rs2149356, rs4986791 and rs5030719) at the TLR4 gene in 155 patients with HCV-related HCC, 153 patients with chronic hepatitis C and 390 healthy controls. All were white and most were Spaniards.

Results: (1) rs5030719 was monomorphic and was not further analysed; (2) the rs2149356 T allele carrier state was significantly less frequent in patients with HCC than in healthy controls (OR 0.421, 95% CI 0.285-0.625) and in patients with chronic hepatitis C (OR 0.426, 95% CI 0.236-0.767); (3) the proportion of rs2149356 T allele carriers progressively diminished with increasing clinical stage of HCC; (4) no significant differences were observed for the rs4986791 T allele.

Conclusion: The TLR4 rs2148356 T allele is associated with a reduced risk of HCC and could slow down its clinical progression in HCV-induced chronic liver disease.

MeSH terms

  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology*
  • Chronic Disease
  • Disease Progression
  • Female
  • Genotype
  • Hepatitis C / complications
  • Hepatitis C / genetics
  • Hepatitis C / metabolism*
  • Heterozygote
  • Humans
  • Liver Diseases / genetics
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Spain
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / physiology*

Substances

  • TLR4 protein, human
  • Toll-Like Receptor 4