Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa

Hyokyoung G Hong, Mateus H Gouveia, Martin D Ogwang, Patrick Kerchan, Steven J Reynolds, Constance N Tenge, Pamela A Were, Robert T Kuremu, Walter N Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Xunde Wang, Jiefu Zhou, Thiago Peixoto Leal, Isaac Otim, Ismail D Legason, Hadijah Nabalende, Herry Dhudha, Mediatrix MumiaFrancine S Baker, Temiloluwa Okusolubo, Leona W Ayers, Kishor Bhatia, James J Goedert, Joshua Woo, Michelle Manning, Nathan Cole, Wen Luo, Belynda Hicks, George Chagaluka, W Thomas Johnston, Nora Mutalima, Eric Borgstein, George N Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M Molyneux, Robert Newton, Amy Hutchinson, Meredith Yeager, Adebowale A Adeyemo, Swee Lay Thein, Charles N Rotimi, Stephen J Chanock, Ludmila Prokunina-Olsson, Sam M Mbulaiteye

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Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

Original languageEnglish
Pages (from-to)113-123
JournalAmerican journal of hematology
Issue number1
Early online date27 Nov 2023
Publication statusPublished - 18 Dec 2023

Bibliographical note

© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

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