Evaluating the Causal Link Between Malaria Infection and Endemic Burkitt Lymphoma in Northern Uganda: A Mendelian Randomization Study

Ismail D. Legason, Ruth M. Pfeiffer, Krizia Ivana Udquim, Andrew W. Bergen, Mateus H. Gouveia, Samuel Kirimunda, Isaac Otim, Eric Karlins, Patrick Kerchan, Hadijah Nabalende, Ariunaa Bayanjargal, Benjamin Emmanuel, Paul Kagwa, Ambrose O. Talisuna, Kishor Bhatia, Meredith Yeager, Robert J. Biggar, Leona W. Ayers, Steven J. Reynolds, James J. GoedertMartin D. Ogwang, Joseph F. Fraumeni, Ludmila Prokunina-Olsson, Sam M. Mbulaiteye

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalEBioMedicine
Volume25
DOIs
StatePublished - Nov 2017
Externally publishedYes

Keywords

  • Burkitt Lymphoma
  • Malaria
  • Malaria resistance genes
  • Mendelian randomization
  • Plasmodium falciparum
  • Sickle cell trait

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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