Epstein-Barr Virus Antibody Titers Are Not Associated with Gastric Cancer Risk in East Asia

Dig Dis Sci. 2018 Oct;63(10):2765-2772. doi: 10.1007/s10620-018-5154-9. Epub 2018 Jun 8.


Background: Epstein-Barr virus (EBV)-positive gastric cancers represent a distinct subtype of gastric cancers and account for nearly 10% of the gastric cancer burden, yet risk detection strategies for this cancer subtype are lacking.

Methods: We conducted a nested case-control study where we assayed 4 EBV antigens [viral capsid antigen (VCA), early antigen (EA), Epstein-Barr nuclear antigen (EBNA), and BZLF1-encoded replication activator protein (ZEBRA)] in either sera or plasma from 1447 gastric cancer cases and 1797 controls obtained from seven prospective cohorts representing individuals from the high gastric cancer-risk countries of China, Japan, and Korea.

Results: The prevalence of EBV sero-positivity was universal with the exception of one sero-negative individual, and the highest titers of the EBV antigens VCA (OR 0.95, 95% CI 0.78-1.17), EBNA (OR 0.88, 95% CI 0.72-1.08), EA (OR 0.97, 95% CI 0.79-1.19), and ZEBRA (OR 0.87, 95% CI 0.71-1.07) were not associated with risk of incident gastric cancer. When we stratified these data by H. pylori status, there was no change in the association.

Conclusions: Multiplex serology of the aforementioned EBV antigens in serum may not be a suitable biomarker for predicting gastric cancer risk in East Asian populations.

Keywords: Epstein–Barr virus; Gastric cancer; Multiplex serology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Viral / analysis*
  • Case-Control Studies
  • Epstein-Barr Virus Infections* / diagnosis
  • Epstein-Barr Virus Infections* / epidemiology
  • Female
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Republic of Korea / epidemiology
  • Risk Assessment
  • Serologic Tests / methods
  • Stomach Neoplasms* / epidemiology
  • Stomach Neoplasms* / immunology
  • Tumor Virus Infections / epidemiology


  • Antigens, Viral