TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals

J Med Virol. 2016 Sep;88(9):1587-95. doi: 10.1002/jmv.24501. Epub 2016 Mar 21.

Abstract

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: cytokines; hepatitis c virus; inflammation; interleukin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Inflammation
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • IL10 protein, human
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10