1. Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.
- Author
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Hong HG, Gouveia MH, Ogwang MD, Kerchan P, Reynolds SJ, Tenge CN, Were PA, Kuremu RT, Wekesa WN, Masalu N, Kawira E, Kinyera T, Wang X, Zhou J, Leal TP, Otim I, Legason ID, Nabalende H, Dhudha H, Mumia M, Baker FS, Okusolubo T, Ayers LW, Bhatia K, Goedert JJ, Woo J, Manning M, Cole N, Luo W, Hicks B, Chagaluka G, Johnston WT, Mutalima N, Borgstein E, Liomba GN, Kamiza S, Mkandawire N, Mitambo C, Molyneux EM, Newton R, Hutchinson A, Yeager M, Adeyemo AA, Thein SL, Rotimi CN, Chanock SJ, Prokunina-Olsson L, and Mbulaiteye SM
- Subjects
- Humans, Africa, Eastern, Alleles, Nectins metabolism, Burkitt Lymphoma epidemiology, Burkitt Lymphoma genetics, Malaria, Malaria, Falciparum epidemiology, Malaria, Falciparum genetics, Malaria, Falciparum complications, Sickle Cell Trait epidemiology, Sickle Cell Trait genetics, Sickle Cell Trait complications
- Abstract
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., (© 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.)
- Published
- 2024
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