Epstein-Barr virus and Burkitt's lymphoma worldwide: the causal relationship revisited

Abstract

Burkitt's lymphoma (BL) in tropical Africa represents by far the most common tumour in children between 0 and 14 years of age, 97% of the tumours being associated with Epstein-Barr virus (EBV). In North Africa, the tumour is about ten times less frequent than in equatorial Africa, but, according to reports from Algeria, 85% of the cases appear to be associated with EBV. In Western countries, BL represents about 3% of childhood tumours, 10 to 15% of them EBV-associated. Thus, from the northern industrialized countries to the equatorial developing countries, increasing incidences of lymphomas of the BL type are paralleled by an increasing proportion of EBV-associated cases. The Ugandan BL prospective study showed that high antibody titres to viral capsid antigen (VCA) preceded BL development by many years, with a quantifiable relationship between the level of VCA antibodies and tumour risk. If an early and/or massive EBV primary infection seems to represent the critical event for BL development in equatorial Africa, the favourable conditions for EBV-associated tumours in North Africa and in Europe remain to be investigated. Malaria appears to favour BL development through an EBV-specific T-cell immune deficiency. Chromosomal translocations and oncogene activation, considered as the final step in lymphoma development, do not appear to be related to EBV. Intervention against the virus may represent the ultimate proof of a causal relationship between EBV and the majority of BL cases around the world.