Serological Response to Epstein-Barr Virus Early Antigen is Associated with Gastric Cancer and Human Immunodeficiency Virus Infection in Zambian Adults: a Case-control Study

Introduction: Gastric cancer is one of the major causes of cancer related deaths, but data from sub-Saharan Africa are very scanty. The cancer genome atlas (TCGA) initiative confirmed Epstein-Barr virus (EBV) related cancer as a distinct subtype, and we set out to look for serological evidence of its role in a sub-Saharan African patient group.

Methods: We used stored serum samples obtained from a gastric cancer case-control study conducted between 2010 and 2012 in Lusaka, Zambia. A total of 147 patients were included with 51 gastric adenocarcinoma cases and 96 age and sex matched controls. The presence of antibodies to EBV nuclear antigen-1 (EBNA-1) and early antigen (EA) was determined using commercially available ELISA kits. Data were analysed in STATA Stata Corp, College Station TX.

Results: Over 90% of all the samples analysed were positive for antibodies to EBNA-1. The presence of antibodies to EBV EA was significantly higher in gastric cancer cases than in controls, (OR 4.38; 95% CI 1.53-13.06, P = 0.0027), with an attributable risk of 23%. HIV infection was also associated with EBV EA seroprevalence (OR 10.97; 95% CI 2.26 -13.06, P = 0.001) but not EBNA-1 (OR 0.81; 95% CI 0.10 -38.75, P = 0.596). There was no association of EBV infection with age below 45 years, Helicobacter pylori infection, intestinal metaplasia, gastric atrophy or inflammation.

Conclusion: We therefore conclude that EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.