Malaria infection linked to childhood cancer risk

New data published in The Journal of Immunology uncovered the role of Plasmodium falciparum infection (malaria) in the development of Burkitt lymphoma (BL), the most common childhood cancer in equatorial Africa and New Guinea. BL has been associated with P. falciparum malaria since 1958, but the underlying mechanism of how this led to cancer remained a mystery. 

"Knowing that malaria has a direct role in increasing childhood cancer risk means that measures to reduce the burden of P. falciparum malaria in Africa could also reduce the incidence of Burkitt lymphoma," shared Dr. Rosemary Rochford, Distinguished Professor of Immunology and Microbiology at the University of Colorado Anschutz School of Medicine, who led the study. 

BL is a cancer that affects B cells, important cells of the immune system that produce antibodies. While BL is a rare cancer globally, its prevalence is ten times higher in areas with a consistent presence of P. falciparum malaria. Five different species of Plasmodium can cause malaria in humans, but only P. falciparum is associated with BL. 

This study found significant elevated expression of an enzyme called AID (activation-induced cytidine deaminase) in B cells during P. falciparum malaria in children. According to the researchers, this pointed to the direct role of P. falciparum malaria in BL due to the role of AID in the development of BL. 

A hallmark of BL is the translocation of a gene called MYC, a genetic mutation where DNA breaks off one chromosome and attaches to another. The enzyme AID is essential for MYC translocation, which is why its presence in malaria patients indicates P. falciparum malaria's role in BL. 

This study assessed blood from children with uncomplicated malaria for AID levels and compared them to children without malaria. Uncomplicated malaria is when a patient's symptoms are non-specific, including fever, chills, sweating, headache, nausea, and/or vomiting, without signs of severe organ dysfunction. AID was significantly elevated in B cells of children with uncomplicated malaria and found to be fully functional. The functionality of the excess AID also supports the role of P. falciparum in causing BL. 

Dr. Rochford hopes "this study adds to the body of literature pointing to a critical role of the enzyme, AID, in the etiology of Burkitt lymphoma and potentially in other non-Hodgkin's lymphomas."

Dr. Rochford and her team are continuing this work by evaluating other effects of P. falciparum on immune function in children and how that creates a permissive environment for cancer.