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

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.