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

Ezequiel M. Fuentes-Pananá,Carmen Maldonado-Bernal,Norma Sánchez-Zauco,María G. Cárdenas-Mondragón,Javier Torres,Alejandro Gómez-Delgado,Margarita Camorlinga-Ponce

doi:10.1155/2017/7069242

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.

Highlights

952,000 new cases of gastric cancer (GC) were estimated in 2012 in the world, and with 723,000 deaths, GC is the third cause of death from cancer worldwide [1, 2]
The study included 127 adult patients with GC, 46 with nonatrophic gastritis, and 197 healthy blood donors that were incorporated as controls
We have previously reported an association between viral capsid antigen (VCA)-IgG antibodies and the intestinal type of GC with a different cohort of patients [18]

Summary

Introduction

952,000 new cases of gastric cancer (GC) were estimated in 2012 in the world, and with 723,000 deaths, GC is the third cause of death from cancer worldwide [1, 2]. GC is thought to have an infectious origin, with Helicobacter pylori (HP) and Epstein-Barr virus (EBV) considered the main associated pathogens [7,8,9,10]. HP is considered the main risk factor to develop GC, with most studies supporting a direct transforming role for EBV in only about 10% of cases. 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. 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

Methods

Results

Discussion

Conclusion