Author:
- Introduction
- Materials and Methods
- Results
- Clinical, demographic, and laboratory characteristics of the study participants.
- IL-10 polymorphisms (-1082A/G, -819C/T, and -592C/A) and eBL.
- IL-6 polymorphism (-174G/C) and eBL.
- IL-10 (-1082A/G, -819C/T, and -592C/A) haplotypes and eBL.
- IL-6 (-174G/C) and IL-10 (-1082A/G, -819C/T, and -592C/A) polymorphisms and EBV load.
- IL-10 haplotypes and EBV loads.
- Discussion
- Conclusion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Bhatia K, Huppi K, Spangler G, Siwarski D, Iyer R, Magrath I, 1993. Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas. Nat Genet 5: 56ā61.
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2.
Brady G, MacArthur GJ, Farrell PJ, 2007. Epstein-Barr virus and Burkitt lymphoma. J Clin Pathol 60: 1397ā1402.
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Bishop PC, Rao VK, Wilson WH, 2000. Burkitt's lymphoma: molecular pathogenesis and treatment. Cancer Invest 18: 574ā583.
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Rainey JJ, Omenah D, Sumba PO, Moormann AM, Rochford R, Wilson ML, 2007. Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya. Int J Cancer 120: 121ā127.
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Bornkamm GW, 2009. Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions than answers. Int J Cancer 124: 1745ā1755.
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Ogden CA, Pound JD, Batth BK, Owens S, Johannessen I, Wood K, Gregory CD, 2005. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt's lymphoma. J Immunol 174: 3015ā3023.
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Cordano P, Lake A, Shield L, Taylor GM, Alexander FE, Taylor PRA, White J, Jarrett RF, 2005. Effect of IL-6 promoter polymorphism on incidence and outcome in Hodgkin's lymphoma. Br J Haematol 128: 493ā495.
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Benjamin D, Knobloch TJ, Dayton MA, 1992. Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. Blood 80: 1289ā1298.
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Stewart JP, Behm FG, Arrand JR, Rooney CM, 1994. Differential expression of viral and human interleukin-10 (IL-10) by primary B cell tumors and B cell lines. Virology 200: 724ā732.
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Cunningham LM, Chapman C, Dunstan R, Bell MC, Joske DJL, 2003. Polymorphisms in the interleukin 10 gene promoter are associated with susceptibility to aggressive non-Hodgkin's lymphoma. Leuk Lymphoma 44: 251ā255.
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Liu J, Song B, Bai X, Liu W, Li Z, Wang J, Zheng Y, Wang Z, 2010. Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese. BMC Cancer 10: 456.
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Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL, 2003. Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 88: 255ā259.
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Wang J, Ding Q, Shi Y, Cao Q, Qin C, Zhu J, Chen J, Yin C, 2011. The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis. Mutagenesis 27: 305ā312.
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Gourley IS, Kurtis JD, Kamoun M, Amon JJ, Duffy PE, 2002. Profound bias in interferon-Ī³ and interleukin-6 allele frequencies in western Kenya, where severe malarial anemia is common in children. J Infect Dis 186: 1007ā1012.
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Baran W, Szepietowski JC, Mazur G, Baran E, 2008. IL-6 and IL-10 promoter gene polymorphisms in psoriasis vulgaris. Acta Derm Venereol 88: 113ā116.
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Ouma C, Davenport GC, Were T, Otieno MF, Hittner JB, Vulule JM, Martinson J, Ong'echa JM, Ferrell RE, Perkins DJ, 2008. Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production. Hum Genet 124: 515ā524.
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Interleukin-6 and Interleukin-10 Gene Promoter Polymorphisms and Risk of Endemic Burkitt Lymphoma
Cliff I. Oduor
Cliff I. Oduor
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Kiprotich Chelimo
Kiprotich Chelimo
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Collins Ouma
Collins Ouma
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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David H. Mulama
David H. Mulama
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Joslyn Foley
Joslyn Foley
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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John Vulule
John Vulule
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Jeffrey A. Bailey
Jeffrey A. Bailey
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Ann M. Moormann
Ann M. Moormann
Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts
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Overexpression of interleukin-6 (IL-6) and IL-10 in endemic Burkitt lymphoma (eBL) may facilitate tumorigenesis by providing a permissive cytokine milieu. Promoter polymorphisms influence interindividual differences in cytokine production. We hypothesized that children genetically predisposed for elevated cytokine levels may be more susceptible to eBL. Using case-control samples from western Kenya consisting of 117 eBL cases and 88 ethnically matched healthy controls, we tested for the association between eBL risk and IL-10 (rs1800896, rs1800871, and rs1800872) and IL-6 (rs1800795) promoter single nucleotide polymorphisms (SNPs) as well as IL-10 promoter haplotypes. In addition, the association between these variants and Epstein Barr Virus (EBV) load was examined. Results showed that selected IL-10 and IL-6 promoter SNPs and IL-10 promoter haplotypes were not associated with risk eBL or EBV levels in EBV-seropositive children. Findings from this study reveal that common variants within the IL-10 and IL-6 promoters do not independently increase eBL risk in this vulnerable population.
Author Notes
Financial support: This work was supported by National Institutes of Health Grants 1KL2RR031981 (to J.A.B.), R01AI099473 (to J.A.B.), and R01CA134051 (to A.M.M.) and the Thrasher Research Fund (to A.M.M.).
Authors' addresses: Cliff I. Oduor and Collins Ouma, Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya, E-mails: cisayaoduor@gmail.com and collinouma@yahoo.com. Kiprotich Chelimo, Department of Biomedical Sciences and Technology, Maseno University, Maseno, Kenya, and Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya, E-mail: chelimokiprotich@gmail.com. David H. Mulama and John Vulule, Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya, E-mails: dmulama@gmail.com and jvulule@gmail.com. Joslyn Foley, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, E-mail: joslyn.foley@umassmed.edu. Jeffrey A. Bailey, Department of Medicine, Division of Transfusion, and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, E-mail: jeffrey.bailey@umassmed.edu.
- Introduction
- Materials and Methods
- Results
- Clinical, demographic, and laboratory characteristics of the study participants.
- IL-10 polymorphisms (-1082A/G, -819C/T, and -592C/A) and eBL.
- IL-6 polymorphism (-174G/C) and eBL.
- IL-10 (-1082A/G, -819C/T, and -592C/A) haplotypes and eBL.
- IL-6 (-174G/C) and IL-10 (-1082A/G, -819C/T, and -592C/A) polymorphisms and EBV load.
- IL-10 haplotypes and EBV loads.
- Discussion
- Conclusion
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Bhatia K, Huppi K, Spangler G, Siwarski D, Iyer R, Magrath I, 1993. Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas. Nat Genet 5: 56ā61.
-
2.
Brady G, MacArthur GJ, Farrell PJ, 2007. Epstein-Barr virus and Burkitt lymphoma. J Clin Pathol 60: 1397ā1402.
-
3.
Bishop PC, Rao VK, Wilson WH, 2000. Burkitt's lymphoma: molecular pathogenesis and treatment. Cancer Invest 18: 574ā583.
-
4.
Rainey JJ, Omenah D, Sumba PO, Moormann AM, Rochford R, Wilson ML, 2007. Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya. Int J Cancer 120: 121ā127.
-
5.
Bornkamm GW, 2009. Epstein-Barr virus and the pathogenesis of Burkitt's lymphoma: more questions than answers. Int J Cancer 124: 1745ā1755.
-
6.
Orem J, Mbidde EK, Lambert B, de Sanjose S, Weiderpass E, 2007. Burkitt's lymphoma in Africa, a review of the epidemiology and etiology. Afr Health Sci 7: 166ā175.
-
7.
Iversen OH, Iversen U, Ziegler JL, Bluming AZ, 1974. Cell kinetics in Burkitt lymphoma. Eur J Cancer 10: 155ā163.
-
8.
ChĆŖne A, Donati D, Guerreiro-Cacais AO, Levitsky V, Chen Q, Falk KI, Orem J, Kironde F, Wahlgren M, Bejarano MT, 2007. A molecular link between malaria and epstein-barr virus reactivation. PLoS Pathog 3: e80.
-
9.
Epstein MA, 1984. Burkitt's lymphoma: clues to the role of malaria. Nature 312: 398.
-
10.
Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, Rosolowski M, Ammerpohl O, Wagener R, Bernhart S, Lenze D, Szczepanowski M, Paulsen M, Lipinski S, Russell R, Adam-Klages S, Apic G, Claviez A, Hasenclever D, Hovestadt V, Hornig N, Korbel J, Kube D, Langenberger D, Lawerenz C, Lisfeld J, Meyer K, Picelli S, Pischimarov J, Radlwimmer B, Rausch T, Rohde M, Schilhabel M, Scholtysik R, Spang R, Trautmann H, Zenz T, Borkhardt A, Drexler H, Mƶller P, MacLeod R, Pott C, Schreiber S, TrĆ¼mper L, Loeffler M, Stadler P, Lichter P, Eils R, KĆ¼ppers R, Hummel M, Klapper W, Rosenstiel P, Rosenwald A, Brors B, Siebert R; MMML-Seq Project ICGC, 2012. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet 44: 1316ā1320.
-
11.
Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards K, Dunphy C, Choi W, Srivastava G, Lugar P, Rizzieri D, Lagoo A, Bernal-Mizrachi L, Mann K, Flowers C, Naresh K, Evens A, Chadburn A, Gordon L, Czader M, Gill J, Hsi E, Greenough A, Moffitt A, McKinney M, Banerjee A, Grubor V, Levy S, Dunson D, Dave S, 2012. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 44: 1321ā1325.
-
12.
Howell WM, Rose-Zerilli MJ, 2007. Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutr 137: 194Sā199S.
-
13.
Lech-Maranda E, Baseggio L, Bienvenu J, Charlot C, Berger F, Rigal D, Warzocha K, Coiffier B, Salles G, 2004. Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. Blood 103: 3529ā3534.
-
14.
Cooper M, Caligiuri M, 2003. Cytokines and Cancer. The Cytokine Handbook (Fourth Edition). Elsevier Ltd., Academic Press, 1213ā1232. ISBN: 978-0-12-689663-3.
-
15.
Ogden CA, Pound JD, Batth BK, Owens S, Johannessen I, Wood K, Gregory CD, 2005. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt's lymphoma. J Immunol 174: 3015ā3023.
-
16.
Yokoi T, Miyawaki T, Yachie A, Kato K, Kasahara Y, Taniguchi N, 1990. Epstein-Barr virus-immortalized B cells produce IL-6 as an autocrine growth factor. Immunology 70: 100ā105.
-
17.
Cordano P, Lake A, Shield L, Taylor GM, Alexander FE, Taylor PRA, White J, Jarrett RF, 2005. Effect of IL-6 promoter polymorphism on incidence and outcome in Hodgkin's lymphoma. Br J Haematol 128: 493ā495.
-
18.
Benjamin D, Knobloch TJ, Dayton MA, 1992. Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. Blood 80: 1289ā1298.
-
19.
Stewart JP, Behm FG, Arrand JR, Rooney CM, 1994. Differential expression of viral and human interleukin-10 (IL-10) by primary B cell tumors and B cell lines. Virology 200: 724ā732.
-
20.
Cunningham LM, Chapman C, Dunstan R, Bell MC, Joske DJL, 2003. Polymorphisms in the interleukin 10 gene promoter are associated with susceptibility to aggressive non-Hodgkin's lymphoma. Leuk Lymphoma 44: 251ā255.
-
21.
Liu J, Song B, Bai X, Liu W, Li Z, Wang J, Zheng Y, Wang Z, 2010. Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese. BMC Cancer 10: 456.
-
22.
Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL, 2003. Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 88: 255ā259.
-
23.
Wang J, Ding Q, Shi Y, Cao Q, Qin C, Zhu J, Chen J, Yin C, 2011. The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis. Mutagenesis 27: 305ā312.
-
24.
Gourley IS, Kurtis JD, Kamoun M, Amon JJ, Duffy PE, 2002. Profound bias in interferon-Ī³ and interleukin-6 allele frequencies in western Kenya, where severe malarial anemia is common in children. J Infect Dis 186: 1007ā1012.
-
25.
Baran W, Szepietowski JC, Mazur G, Baran E, 2008. IL-6 and IL-10 promoter gene polymorphisms in psoriasis vulgaris. Acta Derm Venereol 88: 113ā116.
-
26.
Ouma C, Davenport GC, Were T, Otieno MF, Hittner JB, Vulule JM, Martinson J, Ong'echa JM, Ferrell RE, Perkins DJ, 2008. Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production. Hum Genet 124: 515ā524.
-
27.
Burkitt D, 1962. A lymphoma syndrome in African children. Ann R Coll Surg Engl 30: 211ā219.
-
28.
Burkitt D, O'Conor G, 1961. Malignant lymphoma in African children. I. A clinical syndrome. Cancer 14: 258ā269.
-
29.
Cozen W, Gill PS, Ingles SA, Masood R, MartĆnez-Maza O, Cockburn MG, Gauderman WJ, Pike MC, Bernstein L, Nathwani BN, Salam MT, Danley KL, Wang W, Gage J, Gundell-Miller S, Mack TM, 2004. IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma. Blood 103: 3216ā3221.
-
30.
LĆ³pez RVM, Zago MA, Eluf-Neto J, Curado MP, Daudt AW, da Silva-Junior WA, Zanette DL, Levi JE, de Carvalho MB, Kowalski LP, AbrahĆ£o M, de GĆ³is-Filho JF, Boffetta P, WĆ¼nsch-Filho V, 2011. Education, tobacco smoking, alcohol consumption, and IL-2 and IL-6 gene polymorphisms in the survival of head and neck cancer. Braz J Med Biol Res 44: 1006ā1012.
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