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Title: | Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa |
Authors: | Hong, Hyokyoung G. Gouveia, Mateus H. Ogwang, Martin D. Kerchan, Patrick Reynolds, Steven J. Tenge, Constance N. Were, Pamela A. Kuremu, Robert T. Wekesa, Walter N. Masalu, Nestory Kawira, Esther Kinyera, Tobias Wang, Xunde Zhou, Jiefu Leal, Thiago Peixoto Otim, Isaac . Legason, Ismail D Nabalende, Hadijah Dhudha, Herry Mumia, Mediatrix . Baker, Francine S Okusolubo, Temiloluwa Ayers, Leona W. Bhatia, Kishor Goedert, James J. Woo, Joshua Manning, Michelle Cole, Nathan Luo, Wen Hicks, Belynda Chagaluka, George Johnston, Thomas Mutalima, Nora Borgstein, Eric Liomba, George N. Kamiza, Steve Mkandawire, Nyengo Mitambo, Collins Molyneux, Elizabeth M. Newton, Robert Hutchinson, Amy Yeager, | Meredith Adeyemo, Adebowale A. Thein, Swee Lay Rotimi, Charles N. Chanock, Stephen J. Prokunina-Olsson, Ludmila Mbulaiteye, Sam M. |
Keywords: | Burkitt lymphoma (BL) Childhood cancer Plasmodium falciparum Malaria |
Issue Date: | 23-Oct-2023 |
Publisher: | Wiley |
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 poly- morphisms 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 infec- tion 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. |
URI: | http://ir.mu.ac.ke:8080/jspui/handle/123456789/9393 |
Appears in Collections: | School of Medicine |
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