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 Mumia; Francine 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

doi:10.1002/ajh.27149

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

Health Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	113-123
Journal	American journal of hematology
Volume	99
Issue number	1
Early online date	27 Nov 2023
DOIs	https://doi.org/10.1002/ajh.27149
Publication status	Published - 18 Dec 2023

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Hong, H. G., Gouveia, M. H., Ogwang, M. D., Kerchan, P., Reynolds, S. J., Tenge, C. N., Were, P. A., Kuremu, R. T., Wekesa, W. N., Masalu, N., Kawira, E., Kinyera, T., Wang, X., Zhou, J., Leal, T. P., Otim, I., Legason, I. D., Nabalende, H., Dhudha, H., ... Mbulaiteye, S. M. (2023). Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa. American journal of hematology, 99(1), 113-123. https://doi.org/10.1002/ajh.27149

@article{74ee868f900344d8b426a2a6d47597f4,

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

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.",

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

note = "{\textcopyright} 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.",

year = "2023",

month = dec,

day = "18",

doi = "10.1002/ajh.27149",

language = "English",

volume = "99",

pages = "113--123",

journal = "American journal of hematology",

issn = "0361-8609",

publisher = "Wiley-Liss Inc.",

number = "1",

}

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 & Mbulaiteye, SM 2023, 'Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa', American journal of hematology, vol. 99, no. 1, pp. 113-123. https://doi.org/10.1002/ajh.27149

TY - JOUR

T1 - Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa

AU - Hong, Hyokyoung G

AU - Gouveia, Mateus H

AU - Ogwang, Martin D

AU - Kerchan, Patrick

AU - Reynolds, Steven J

AU - Tenge, Constance N

AU - Were, Pamela A

AU - Kuremu, Robert T

AU - Wekesa, Walter N

AU - Masalu, Nestory

AU - Kawira, Esther

AU - Kinyera, Tobias

AU - Wang, Xunde

AU - Zhou, Jiefu

AU - Leal, Thiago Peixoto

AU - Otim, Isaac

AU - Legason, Ismail D

AU - Nabalende, Hadijah

AU - Dhudha, Herry

AU - Mumia, Mediatrix

AU - Baker, Francine S

AU - Okusolubo, Temiloluwa

AU - Ayers, Leona W

AU - Bhatia, Kishor

AU - Goedert, James J

AU - Woo, Joshua

AU - Manning, Michelle

AU - Cole, Nathan

AU - Luo, Wen

AU - Hicks, Belynda

AU - Chagaluka, George

AU - Johnston, W Thomas

AU - Mutalima, Nora

AU - Borgstein, Eric

AU - Liomba, George N

AU - Kamiza, Steve

AU - Mkandawire, Nyengo

AU - Mitambo, Collins

AU - Molyneux, Elizabeth M

AU - Newton, Robert

AU - Hutchinson, Amy

AU - Yeager, Meredith

AU - Adeyemo, Adebowale A

AU - Thein, Swee Lay

AU - Rotimi, Charles N

AU - Chanock, Stephen J

AU - Prokunina-Olsson, Ludmila

AU - Mbulaiteye, Sam M

PY - 2023/12/18

Y1 - 2023/12/18

N2 - 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.

AB - 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.

U2 - 10.1002/ajh.27149

DO - 10.1002/ajh.27149

M3 - Article

C2 - 38009642

SN - 0361-8609

VL - 99

SP - 113

EP - 123

JO - American journal of hematology

JF - American journal of hematology

IS - 1

ER -