TY - JOUR
T1 - Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda
T2 - A Mendelian Randomization Study
AU - Legason, Ismail D.
AU - Pfeiffer, Ruth M.
AU - Udquim, Krizia Ivana
AU - Bergen, Andrew W.
AU - Gouveia, Mateus H.
AU - Kirimunda, Samuel
AU - Otim, Isaac
AU - Karlins, Eric
AU - Kerchan, Patrick
AU - Nabalende, Hadijah
AU - Bayanjargal, Ariunaa
AU - Emmanuel, Benjamin
AU - Kagwa, Paul
AU - Talisuna, Ambrose O.
AU - Bhatia, Kishor
AU - Yeager, Meredith
AU - Biggar, Robert J.
AU - Ayers, Leona W.
AU - Reynolds, Steven J.
AU - Goedert, James J.
AU - Ogwang, Martin D.
AU - Fraumeni, Joseph F.
AU - Prokunina-Olsson, Ludmila
AU - Mbulaiteye, Sam M.
N1 - Funding Information:
The study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I ) and, in part, by the Intramural Research Program, National Institute of Allergy and Infectious Diseases (SJR), National Institutes of Health , Department of Health and Human Services . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content of this manuscript is the sole responsibility of the authors.
Funding Information:
The study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI) (Contracts HHSN261201100063C and HHSN261201100007I) and, in part, by the Intramural Research Program, National Institute of Allergy and Infectious Diseases (SJR), National Institutes of Health, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content of this manuscript is the sole responsibility of the authors.
Publisher Copyright:
© 2017
PY - 2017/11
Y1 - 2017/11
N2 - Background Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Methods Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010–2015. We modeled associations between genotypes and eBL or malaria using logistic regression. Findings SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0·37, 95% CI 0·21–0·66; p = 0·0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0·73, 95% CI 0·50–1·07) and -CC genotypes (OR 0·53, 95% CI 0·29–0·95, ptrend = 0·019); IL1A rs2856838-AG (OR 0·56, 95% CI 0·39–0·81) and -AA genotype (OR 0·50, 95% CI 0·28–1·01, ptrend = 0·0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0·57, 95% CI 0·35–0·93, p = 0·0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Interpretation Our results support a causal effect of malaria infection on eBL.
AB - Background Plasmodium falciparum (Pf) malaria infection is suspected to cause endemic Burkitt Lymphoma (eBL), but the evidence remains unsettled. An inverse relationship between sickle cell trait (SCT) and eBL, which supports that between malaria and eBL, has been reported before, but in small studies with low power. We investigated this hypothesis in children in a population-based study in northern Uganda using Mendelian Randomization. Methods Malaria-related polymorphisms (SCT, IL10, IL1A, CD36, SEMA3C, and IFNAR1) were genotyped in 202 eBL cases and 624 controls enrolled during 2010–2015. We modeled associations between genotypes and eBL or malaria using logistic regression. Findings SCT was associated with decreased risk of eBL (adjusted odds ratio [OR] 0·37, 95% CI 0·21–0·66; p = 0·0003). Decreased risk of eBL was associated with IL10 rs1800896-CT (OR 0·73, 95% CI 0·50–1·07) and -CC genotypes (OR 0·53, 95% CI 0·29–0·95, ptrend = 0·019); IL1A rs2856838-AG (OR 0·56, 95% CI 0·39–0·81) and -AA genotype (OR 0·50, 95% CI 0·28–1·01, ptrend = 0·0016); and SEMA3C rs4461841-CT or -CC genotypes (OR 0·57, 95% CI 0·35–0·93, p = 0·0193). SCT and IL10 rs1800896, IL1A rs2856838, but not SEMA3C rs4461841, polymorphisms were associated with decreased risk of malaria in the controls. Interpretation Our results support a causal effect of malaria infection on eBL.
KW - Burkitt Lymphoma
KW - Malaria
KW - Malaria resistance genes
KW - Mendelian randomization
KW - Plasmodium falciparum
KW - Sickle cell trait
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U2 - 10.1016/j.ebiom.2017.09.037
DO - 10.1016/j.ebiom.2017.09.037
M3 - Article
C2 - 29033373
AN - SCOPUS:85031123952
SN - 2352-3964
VL - 25
SP - 58
EP - 65
JO - EBioMedicine
JF - EBioMedicine
ER -