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Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study.
Legason, Ismail D; Pfeiffer, Ruth M; Udquim, Krizia-Ivana; Bergen, Andrew W; Gouveia, Mateus H; Kirimunda, Samuel; Otim, Isaac; Karlins, Eric; Kerchan, Patrick; Nabalende, Hadijah; Bayanjargal, Ariunaa; Emmanuel, Benjamin; Kagwa, Paul; Talisuna, Ambrose O; Bhatia, Kishor; Yeager, Meredith; Biggar, Robert J; Ayers, Leona W; Reynolds, Steven J; Goedert, James J; Ogwang, Martin D; Fraumeni, Joseph F; Prokunina-Olsson, Ludmila; Mbulaiteye, Sam M.
Afiliación
  • Legason ID; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda.
  • Pfeiffer RM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: pfeiffer@mail.nih.gov.
  • Udquim KI; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: krizia-ivana.udquim@nih.gov.
  • Bergen AW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA.
  • Gouveia MH; Instituto de Pesquisa Rene Rachou, Fundação Oswaldo Cruz, 30190-002 Belo Horizonte, Minas Gerais, Brazil.
  • Kirimunda S; Department of Medical Microbiology, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
  • Otim I; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda.
  • Karlins E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: karlinser@mail.nih.gov.
  • Kerchan P; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda.
  • Nabalende H; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda.
  • Bayanjargal A; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Emmanuel B; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda; Benjamin Emmanuel, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: ben.emmanuel@umaryland.edu.
  • Kagwa P; EMBLEM Study, African Field Epidemiology Network, P.O. Box 12874, Kampala, Uganda.
  • Talisuna AO; World Health Organization, Regional Office for Africa, Brazzaville, Congo.
  • Bhatia K; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: kishor.bhatia@cgix.com.
  • Yeager M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: yeagerm@mail.nih.gov.
  • Biggar RJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA.
  • Ayers LW; Department of Pathology, The Ohio State University, Columbus, OH, USA. Electronic address: Leona.Ayers@osumc.edu.
  • Reynolds SJ; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: sreynol6@jhmi.edu.
  • Goedert JJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA.
  • Ogwang MD; EMBLEM Study, St. Mary's Hospital, Lacor, P.O. Box 180, Gulu, Uganda. Electronic address: ogwang.martin@lacorhospital.org.
  • Fraumeni JF; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: fraumenj@exchange.nih.gov.
  • Prokunina-Olsson L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: prokuninal@mail.nih.gov.
  • Mbulaiteye SM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Ctr Dr, Bethesda 20892, MD, USA. Electronic address: mbulaits@mail.nih.gov.
EBioMedicine ; 25: 58-65, 2017 Nov.
Article en En | MEDLINE | ID: mdl-29033373
ABSTRACT

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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfoma de Burkitt / Malaria Falciparum / Predisposición Genética a la Enfermedad / Análisis de la Aleatorización Mendeliana Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Región como asunto: Africa Idioma: En Revista: EBioMedicine Año: 2017 Tipo del documento: Article País de afiliación: Uganda
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfoma de Burkitt / Malaria Falciparum / Predisposición Genética a la Enfermedad / Análisis de la Aleatorización Mendeliana Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Región como asunto: Africa Idioma: En Revista: EBioMedicine Año: 2017 Tipo del documento: Article País de afiliación: Uganda