IARC 60th Anniversary - 19-21 May 2026
Session : Cancer Epigenetics: Unraveling Aetiology and Mechanisms to Advance Prevention
Unravelling the synergistic impact of exposures to mycotoxins and Epstein Barr virus at early stages of Burkitt lymphomagenesis.
KHOUEIRY R. 1,8, MOUCHTARIS-MICHAILIDIS T. 1,2,8,10, TRUONG N. 1,2,10, AKINYI ODONGO G. 1, MAROUI M. 3, MUNDO l. 4, MANARA F. 1, CAHAIS V. 1,8, SALLÉ A. 1, CUENIN C. 1,8, BOUAOUN L. 8, TOE L. 5,9, DAILEY-CHWALIBOG T. 6,9, BOUDA C. 7, LACHAT C. 9, GRUFFAT H. 3, ACCARDI R. 1, DE SAEGER S. 2,10, GHEIT T. 1,11, DE BOEVRE M. 2,10, HERCEG Z. 1
1 Epigenomics and Mechanisms Branch, International agency for research on cancer, Lyon, France; 2 Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; 3 Centre International de Recherche e infectiologie (CIRI), Lyon , France; 4 Department of Medical Biotechnology, Section of Pathology, University of Sienna, Siena , Italy; 5 Unité Nutrition et Maladies Métaboliques, Institut de Recherche en Sciences de la Santé (IRSS) , Bobo-Dioulasso, Burkina Faso; 6 Agence de Formation de Recherche et d’Expertise en Santé pour l’Afrique (AFRICSanté), Bobo-Dioulasso, Burkina Faso; 7 Department of pediatric oncology, Hopital Yalgado Ouedraogo, Ouagadougou, Burkina Faso; 8 Environemental and lifestyle epidemiology branch, International agency for Research on Cancer, Lyon, France; 9 Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium; 10 Cancer Research Institute Ghent, CRIG, Ghent, Belgium; 11 Early Detection, Prevention, and Infections Branch (EPR), International Agency for Research on Cancer, Lyon , France
Background
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub-Saharan Africa. While Epstein–Barr virus (EBV) infection is a necessary factor in eBL development, it is insufficient on its own to drive oncogenesis, indicating the involvement of additional cofactors. In eBL-endemic regions, children are chronically exposed to mycotoxins—toxic fungal metabolites contaminating staple foods—from in utero life through early childhood. Mycotoxins are known to alter immune function and epigenetic regulation, yet their interaction with EBV and contribution to eBL pathogenesis remain poorly understood.
Objectives
We hypothesize that in utero and early-life co-exposure to mycotoxins and EBV synergistically disrupts immune and epigenetic regulation, creating a permissive environment for eBL development. Our objectives were to (i) investigate the combined effects of mycotoxins and EBV on the epigenome during early life, (ii) identify molecular mechanisms through which mycotoxins enhance EBV-associated oncogenic processes, and (iii) uncover early biomarkers of harmful co-exposures relevant to eBL risk.
Methods
We applied a dual molecular epidemiology and experimental approach. First, we leveraged a longitudinal mother–child cohort from rural Burkina Faso to assess prenatal and early-life exposure to mycotoxins and EBV infection. Mycotoxin levels were measured in biological samples, EBV infection status was assessed, and genome-wide DNA methylation analyses were performed in infant blood samples. Second, we conducted functional studies using human B cells and humanized mouse models to investigate mechanistic interactions between EBV and mycotoxins, focusing on epigenetic and transcriptional alterations.
Results
Ochratoxin A (OTA) was the most prevalent mycotoxin detected and was significantly associated with EBV infection. Epigenome-wide analyses identified 1,615 differentially methylated regions (DMRs) associated with OTA exposure and 8,663 DMRs linked to EBV infection, with combined exposure amplifying epigenetic alterations. Affected pathways were enriched for immune regulation and cancer-related functions and overlapped with known BL-associated methylation patterns. Functional studies revealed that aflatoxin B1 (AFB1) and EBV synergistically induced the immunomodulatory chemokine CCL22 in B cells through NF-κB activation, mediated in part by EBV latent proteins such as LMP1. Elevated CCL22 enhanced EBV infection and viral gene expression, while neutralization of CCL22 significantly restricted EBV infection and dissemination both in vitro and in vivo.
Conclusions / Implications
Our findings reveal novel mechanisms by which early-life mycotoxin exposure and EBV infection interact to drive immune and epigenetic alterations relevant to eBL development. These results provide biological plausibility for the high incidence of eBL in regions with chronic mycotoxin-contaminated food supplies and highlight mycotoxins as modifiable environmental risk factors. Identifying early biomarkers and mechanistic pathways opens new avenues for cancer prevention strategies targeting food safety and early-life exposures in vulnerable populations.