Abstract 60: Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa

Abstract Purpose: Epstein Barr virus (EBV) is a viral carcinogen associated with Burkitt lymphoma (BL), an aggressive lymphoma that is rare in the U.S. but responsible for most childhood cancer in the equatorial regions of sub-Saharan Africa. EBV is also associated with other cancers, including nasopharyngeal carcinoma in south Asia, some types of gastric cancer, and Hodgkin lymphoma, which contribute to about 2% of the global cancer burden. Discovery of antibody profiles associated with BL would provide new ways to investigate the biology of EBV-associated malignancies, design of screening or diagnostic assays, or develop targeted approaches for treatment. Here, we used an EBV proteome-wide assessment of seroprofiles against EBV in well-characterized cases and controls in the EMBLEM study. Methods: We measured antibody responses against a panel of 199 EBV recombinant proteins expressed from 5 EBV strains (48.2% ag876, 19.1% b958, 18.6% mutu, 9.6% akata, and raji 4.5%) in 701 BL cases and 700 age-, sex-, and area-frequency matched community controls from six regions Kenya, Tanzania, and Uganda. EBV peptide reactivity (standardized signal intensity, SSI) and positivity (number of positive peptides as defined as SSI ≥1) in cases and controls were compared via student’s unpaired t-tests and chi-squared test. Odds ratios of association and 95% confidence intervals were generated by logistic regression models, controlling for sex, country of origin, and by age group. Statistical significance was based on Bonferroni adjusted p-values. Results: Overall, BL cases were more likely to have higher mean (SD) peptide reactivity [case: 209.0 (25.5); control:198.1 (24.0); SSI, p=3.8e-16] and mean (SD) number of seropositive EBV peptides [case:95.9 (35.8); control: 83.0 (34.2); p=7.7e-12] as compared to controls. Total reactivity and seropositivity of peptides from all strains was significantly higher in cases as compared to controls, except for the Akata strain. We identified 66 peptides with mean values significantly higher in BL cases than controls after Bonferroni correction (range of ORs:1.53–4.07), of which 53 showed a significant trend (range of ORs: 1.27–2.28). These EBV peptides were mostly in the late lytic and latent stages of infection. Conclusion: Our results suggest that EBV peptides involved in both latency and lytic replication may influence BL pathogenesis, making them suitable targets for BL prevention and control. Citation Format: Jacquelyn R. Bedsaul-Fryer, Carla Proietti, Martin D. Ogwang, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert K. Tenge, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Hadijah Nabalende, Herry Dhudha, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Hyokyoung G. Hong, Denise Doolan, Sam M. Mbulaiteye. Discovery of Epstein-Barr Virus Antibody Seroprofiles Associated with Burkitt Lymphoma Risk in East Africa [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 60.