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

被引：37

作者：

Legason, Ismail D. ^{[1
]}

Pfeiffer, Ruth M. ^{[2
]}

Udquim, Krizia-Ivana ^{[3
]}

Bergen, Andrew W. ^{[2
]}

Gouveia, Mateus H. ^{[4
]}

Kirimunda, Samuel ^{[5
]}

Otim, Isaac ^{[1
]}

Karlins, Eric ^{[2
]}

Kerchan, Patrick ^{[1
]}

Nabalende, Hadijah ^{[1
]}

Bayanjargal, Ariunaa ^{[3
]}

Emmanuel, Benjamin ^{[1
,6
]}

Kagwa, Paul ^{[1
]}

Talisuna, Ambrose O. ^{[7
]}

Bhatia, Kishor ^{[2
]}

Yeager, Meredith ^{[2
]}

Biggar, Robert J. ^{[2
]}

Ayers, Leona W. ^{[8
]}

Reynolds, Steven J. ^{[9
]}

Goedert, James J. ^{[2
]}

Ogwang, Martin D. ^{[10
]}

Fraumeni, Joseph F., Jr. ^{[2
]}

Prokunina-Olsson, Ludmila ^{[3
]}

Mbulaiteye, Sam M. ^{[2
]}

机构：

[1] African Field Epidemiol Network, EMBLEM Study, POB 12874, Kampala, Uganda

[2] NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA

[3] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[4] Fundacao Oswaldo Cruz, Inst Pesquisa Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil

[5] Makerere Univ, Coll Hlth Sci, Dept Med Microbiol, POB 7072, Kampala, Uganda

[6] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA

[7] World Hlth Org, Reg Off Africa, Brazzaville, Rep Congo

[8] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA

[9] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[10] St Marys Hosp, EMBLEM Study, POB 180, Lacor, Gulu, Uganda

来源：

EBIOMEDICINE | 2017年 / 25卷

基金：

美国国家卫生研究院;

关键词：

Burkitt Lymphoma; Malaria; Plasmodium falciparum; Mendelian randomization; Sickle cell trait; Malaria resistance genes; SICKLE-CELL TRAIT; EPSTEIN-BARR-VIRUS; FALCIPARUM-MALARIA; GENOME-WIDE; SUSCEPTIBILITY; TRANSMISSION; ASSOCIATION; ANTIBODIES; CHILDREN;

D O I：

10.1016/j.ebiom.2017.09.037

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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, p(trend) = 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, p(trend) = 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.

引用

页码：58 / 65

页数：8

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