Is endemic Burkitt's lymphoma an alliance between three infections and a tumour promoter?

Malaria and Epstein-Barr virus (EBV), recognised cofactors for endemic Burkitt's lymphoma, are ubiquitous within the lymphoma belt of Africa, and, unless other cofactors are involved, the tumour should be much more common than it is. Malaria and EBV alone cannot account for the occasional shifting foci and space-time case clusters of endemic Burkitt's lymphoma. Arboviruses and plant tumour promoters are other possible local cofactors that could explain such characteristics. The geographical and age distributions of endemic Burkitt's lymphoma parallel those of potentially oncogenic, mosquito-borne arboviruses. Arboviruses seem to be associated with case clusters of endemic Burkitt's lymphoma, and symptoms compatible with arbovirus infection have been seen immediately before the onset of the tumour. RNA and DNA viruses, including EBV, are promoted by extracts of a commonly used plant, Euphorbia tirucalli, the distribution of which coincides with the boundaries of the lymphoma belt. Extracts of E tirucalli are tumour promoters and can induce the characteristic 8;14 translocation of endemic Burkitt's lymphoma in EBV-infected cell-lines. They also activate latent EBV in infected cells, enhance EBV-mediated cell transformation, and modulate EBV-specific immunity.