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Acute Leukemias

Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease

Leukemia volume 26, pages 1203–1210 (2012)Cite this article

Abstract

Little is known about the etiology of childhood acute lymphoblastic leukemia (ALL). The presence of atopic disease has been shown to protect against developing childhood ALL. The aim of this study was to examine whether single nucleotide polymorphisms (SNPs) in innate immunity genes previously associated with atopic disease, can elucidate the inverse association between childhood ALL and atopic disease. We studied 525 children, including 192 with childhood ALL, 149 with atopic disease and 184 healthy control subjects. We compared genotype distributions of 29 SNPs in genes of TLR2, TLR4, TLR6, TLR9, TLR10 and CD14 between the three groups and corrected for multiple testing. The genotype distributions of two SNPs in the TLR6 gene, rs5743798 and rs6531666, differed significantly between children with ALL, children with atopic disease and control subjects. Particularly in children with atopic eczema, risk alleles for atopic disease were observed more often than in control subjects, and less often in children with ALL than in control subjects. These findings support the immune surveillance hypothesis as an explanation for the protective association of atopic disease on childhood ALL. Further investigation is warranted to examine in more detail the role of innate immunity in the development of childhood ALL.

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Acknowledgements

We acknowledge the help of Dr Titia Brantsma—van Wulfften Palthe from Utrecht for correcting the English. Moreover, we thank Dr Arjan Lankester for revising the manuscript. The Dutch ODAS foundation supported the work of KGE Miedema. EM te Poele was supported by a research grant from the Foundation for Pediatric Oncology Groningen (SKOG 03-001). The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study is funded by the Netherlands Organization for Health Research and Development, the Netherlands Asthma Foundation, the Netherlands Ministry of Planning, Housing and the Environment, the Netherlands Ministry of Health, Welfare and Sport and the National Institute for Public Health and the Environment.

Author contributions

Karin GE Miedema designed and performed the research, analyzed and interpreted data, performed statistical analysis and wrote the manuscript. Wim JE Tissing designed research, performed research, analyzed and interpreted data and wrote the manuscript. Esther M te Poele designed and performed the research, collected data and revised the manuscript. Willem A Kamps interpreted data and revised the manuscript. Behrooz Z Alizadeh and Marjan Kerkhof analyzed and interpreted data, performed statistical analysis and revised the manuscript. Johan HC de Jongste, Henriëtte A Smit, Anne P de Pagter and Marc Bierings performed research, collected data and revised the manuscript. H Marike Boezen designed research and revised the manuscript. Dirkje S Postma and Eveline SJM de Bont designed the research, interpreted data and revised the manuscript. Gerard H Koppelman designed the research, interpreted data and wrote the manuscript.

Author information

Author notes

  1. W J E Tissing and E M te Poele: These authors contributed equally to this work.

  2. E S J M de Bont and G H Koppelman: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    K G E Miedema, W J E Tissing, E M te Poele, W A Kamps & E S J M de Bont

  2. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    B Z Alizadeh, M Kerkhof & H M Boezen

  3. Department of Pediatrics/Respiratory Medicine, Erasmus University Medical Center—Sophia Children's Hospital, Rotterdam, The Netherlands

    J C de Jongste

  4. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    H A Smit

  5. Department of Pediatric Immunology and Hematology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

    A P de Pagter & M Bierings

  6. Department of Lung Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    D S Postma

  7. Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    G H Koppelman

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  1. K G E Miedema
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Correspondence to W J E Tissing.

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Miedema, K., Tissing, W., te Poele, E. et al. Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease. Leukemia 26, 1203–1210 (2012). https://doi.org/10.1038/leu.2011.341

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