IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa

Francine S. Baker; Jeanny Wang; Oscar Florez- Vargas; Nathan R. Brand; 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; Isaac Otim; Ismail D. Legason; Hadijah Nabalende; George Chagaluka; Nora Mutalima; Eric Borgstein; George N. Liomba; Steve Kamiza; Nyengo Mkandawire; Collins Mitambo; Elizabeth M. Molyneux; Robert Newton; Ludmila Prokunina-Olsson; Sam M. Mbulaiteye

doi:10.1089/jir.2023.0014

IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa

Francine S. Baker, Jeanny Wang, Oscar Florez- Vargas, Nathan R. Brand, 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, Isaac Otim, Ismail D. Legason, Hadijah Nabalende, George Chagaluka, Nora Mutalima, Eric BorgsteinGeorge N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M. Molyneux, Robert Newton, Ludmila Prokunina-Olsson, Sam M. Mbulaiteye

Health Sciences

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

Abstract

Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78 in West sub-Saharan Africa (SSA), compared to 35-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case–control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6–9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

Original language	English
Journal	Journal of Interferon Cytokine Research
DOIs	https://doi.org/10.1089/jir.2023.0014
Publication status	E-pub ahead of print - 27 Jun 2023

Bibliographical note

PMID: 37366802

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10.1089/jir.2023.0014

Cite this

Baker, F. S., Wang, J., Vargas, O. F., Brand, N. R., 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., Otim, I., Legason, I. D., Nabalende, H., Chagaluka, G., Mutalima, N., ... Mbulaiteye, S. M. (2023). IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa. Journal of Interferon Cytokine Research. Advance online publication. https://doi.org/10.1089/jir.2023.0014

@article{e430b54b780c4509bad7f8f2b478138e,

title = "IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa",

abstract = "Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78 in West sub-Saharan Africa (SSA), compared to 35-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case–control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6–9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.",

author = "Baker, {Francine S.} and Jeanny Wang and Vargas, {Oscar Florez-} and Brand, {Nathan R.} 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 Isaac Otim and Legason, {Ismail D.} and Hadijah Nabalende and George Chagaluka 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 Ludmila Prokunina-Olsson and Mbulaiteye, {Sam M.}",

note = "PMID: 37366802",

year = "2023",

month = jun,

day = "27",

doi = "10.1089/jir.2023.0014",

language = "English",

journal = "Journal of Interferon Cytokine Research",

issn = "1079-9907",

publisher = "Mary Ann Liebert Inc.",

}

Baker, FS, Wang, J, Vargas, OF, Brand, NR, Ogwang, MD, Kerchan, P, Reynolds, SJ, Tenge, CN, Were, PA, Kuremu, RT, Wekesa, WN, Masalu, N, Kawira, E, Kinyera, T, Otim, I, Legason, ID, Nabalende, H, Chagaluka, G, Mutalima, N, Borgstein, E, Liomba, GN, Kamiza, S, Mkandawire, N, Mitambo, C, Molyneux, EM, Newton, R, Prokunina-Olsson, L & Mbulaiteye, SM 2023, 'IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa', Journal of Interferon Cytokine Research. https://doi.org/10.1089/jir.2023.0014

TY - JOUR

T1 - IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa

AU - Baker, Francine S.

AU - Wang, Jeanny

AU - Vargas, Oscar Florez-

AU - Brand, Nathan R.

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 - Otim, Isaac

AU - Legason, Ismail D.

AU - Nabalende, Hadijah

AU - Chagaluka, George

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 - Prokunina-Olsson, Ludmila

AU - Mbulaiteye, Sam M.

N1 - PMID: 37366802

PY - 2023/6/27

Y1 - 2023/6/27

N2 - Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78 in West sub-Saharan Africa (SSA), compared to 35-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case–control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6–9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

AB - Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78 in West sub-Saharan Africa (SSA), compared to 35-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case–control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6–9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

U2 - 10.1089/jir.2023.0014

DO - 10.1089/jir.2023.0014

M3 - Article

SN - 1079-9907

JO - Journal of Interferon Cytokine Research

JF - Journal of Interferon Cytokine Research

ER -