biostudies-literatureBroen KUniversity of MichiganSimons FoundationHHS | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (DCEG)University of Michigan (UM)Simons Foundation (SF)HHS | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institutee2211055120https://www.ebi.ac.uk/biostudies/studies/S-EPMC9926229biostudies-literatureUnknown120(2)Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, <i>Plasmodium falciparum</i>, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of <i>P. falciparum</i> infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative <i>P. falciparum</i> exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime <i>P. falciparum</i> infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual <i>P. falciparum</i> infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to <i>P. falciparum</i> malaria and support emphasizing the link between malaria and eBL.Proceedings of the National Academy of Sciences of the United States of AmericaBurkitt lymphoma risk shows geographic and temporal associations with <i>Plasmodium falciparum</i> infections in Uganda, Tanzania, and Kenya.PMC9926229HHSN261201100063C; HHSN261201100007I5 T42 OH 8455-15812255Masalu NBuller IDGoedert JJReynolds SJKinyera TDickens JWekesa WNZelner JWilson MLAyers LWOtim IBiggar RJMbulaiteye SMLegason IDNabalende HBhatia KKuremu RTTenge CNTrangucci RKerchan PBroen KOgwang MDWere PAKawira EfalseBurkitt lymphoma risk shows geographic and temporal associations with <i>Plasmodium falciparum</i> infections in Uganda, Tanzania, and Kenya.Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, <i>Plasmodium falciparum</i>, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of <i>P. falciparum</i> infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative <i>P. falciparum</i> exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime <i>P. falciparum</i> infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual <i>P. falciparum</i> infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to <i>P. falciparum</i> malaria and support emphasizing the link between malaria and eBL.2023-01-01T00:00:00Z2023 Jan2025-04-04T12:41:39.51Z2025-04-04T12:41:39.51ZS-EPMC99262293659567610.1073/pnas.2211055120