Elevated Levels of Interferon- γ Are Associated with High Levels of Epstein-Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer

J Immunol Res. 2017:2017:7069242. doi: 10.1155/2017/7069242. Epub 2017 Nov 14.

Abstract

Background: The inflammatory response directed against Helicobacter pylori (HP) is believed to be one of the main triggers of the appearance of gastric lesions and their progression to gastric cancer (GC). Epstein-Barr virus (EBV) has been found responsible for about 10% of all GCs, but the inflammatory response has not been studied in GC patients with evidence of high levels of EBV reactivation.

Objective: To determine the relationship between inflammation and antibodies against EBV reactivation antigens, HP, and the bacterium virulence factor CagA in patients with GC.

Methods: 127 GC patients, 46 gastritis patients, and 197 healthy subjects were studied. IL-1β, IL-6, IL-8, IL-10, TNF-α, TGF-β, MCP-1, and IFN-γ levels were measured in serum or plasma and compared against the antibody titers of VCA-IgG, HP, and the HP virulence factor CagA. Statistical associations were estimated.

Results: Significant ORs and positive trends were found between VCA-IgG and IFN-γ, specifically for patients with GC of intestinal type (OR: 6.4, 95% C.I. 1.2-35.4) (p < 0.044).

Conclusions: We confirmed a positive association between a marker of EBV reactivation and intestinal gastric cancer and present evidence of a correlation with elevated serum levels of IFN-γ, but not with the other cytokines.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antigens, Bacterial / blood
  • Antigens, Viral / immunology
  • Bacterial Proteins / blood
  • Biomarkers, Tumor / blood
  • Capsid Proteins / immunology
  • Cross-Sectional Studies
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / virology
  • Helicobacter pylori / physiology*
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Interferon-gamma / metabolism*
  • Intestines / pathology*
  • Male
  • Middle Aged
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / virology
  • Up-Regulation
  • Virulence Factors / blood
  • Virus Activation
  • Young Adult

Substances

  • Antibodies, Viral
  • Antigens, Bacterial
  • Antigens, Viral
  • Bacterial Proteins
  • Biomarkers, Tumor
  • Capsid Proteins
  • Epstein-Barr viral capsid antigen
  • Virulence Factors
  • cagA protein, Helicobacter pylori
  • Interferon-gamma