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Acute Leukemias

Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia

Leukemia volume 26, pages 2212–2215 (2012)Cite this article

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Abstract

Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence that common genetic variation influences the risk of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), identifying risk single-nucleotide polymorphisms (SNPs) localizing to 7p12.2, 9p21.3, 10q21.2 and 14q11.2. The testing of SNPs individually for an association in GWA studies necessitates the imposition of a very stringent P-value to address the issue of multiple testing. While this reduces false positives, real associations may be missed and therefore any estimate of the total heritability will be negatively biased. Using GWAS data on 823 BCP-ALL cases by considering all typed SNPs simultaneously, we have calculated that 24% of the total variation in BCP-ALL risk is accounted for common genetic variation (95% confidence interval 6–42%). Our findings provide support for a polygenic basis for susceptibility to BCP-ALL and have wider implications for future searches for novel disease-causing risk variants.

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Acknowledgements

Leukaemia and Lymphoma Research (UK) and the Kay Kendall Leukaemia Fund provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) is also acknowledged. This study made use of control genotyping data generated by the Wellcome Trust Case–Control Consortium. We acknowledge the use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113 and 085475. We are grateful to all the patients and individuals for their participation and we would also like to thank the clinicians, other hospital staff and study staff who contributed to the blood sample and data collection for this study.

WEB ADDRESSES

The URLs for data presented herein are as follows: PLINK: http://pngu.mgh.harvard.edu/purcell/plink/ British 1958 birth cohort: http://www.b58cgene.sgul.ac.uk Ilumina: http://www.illumina.com/ Genome-wide Complex Trait Analysis (GCTA): http://gump.qimr.edu.au/gcta/ Childhood Leukemia International Consortium: https://ccls.berkeley.edu/clic

AUTHOR CONTRIBUTIONS

RSH designed the study; RSH and VE-M drafted the manuscript; VE-M and FJH performed statistical analyses; EP oversaw laboratory analyses; ES and SEK performed curation and sample preparation of MRC ALL 97 trial samples; TL and ER managed and maintained UKCCS sample data; MT performed curation and sample preparation of UKCCS samples; JMA and JAEI performed ascertainment, curation and sample preparation of Northern Institute for Cancer Research case series; RSH and MG obtained funding and designed parent project.

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Authors and Affiliations

  1. Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK

    V Enciso-Mora, F J Hosking & R S Houlston

  2. Yorkshire Regional Genetic Service, St James’s University Hospital, Leeds, UK

    E Sheridan

  3. Department of Paediatric and Adolescent Oncology and Haematology, St James’s University Hospital, Leeds, UK

    S E Kinsey

  4. Department of Health Sciences, Epidemiology and Genetics Unit, University of York, York, UK

    T Lightfoot & E Roman

  5. Northern Institute for Cancer Research, Newcastle University, Framlington Place, Newcastle upon Tyne, UK

    J A E Irving & J M Allan

  6. Wellcome Trust Centre, University of Oxford, Oxford, UK

    I P M Tomlinson

  7. Cancer Immunogenetics Group, School of Cancer and Enabling Sciences, University of Manchester, St Mary's Hospital, Manchester, UK

    M Taylor

  8. Division of Molecular Pathology, The Institute of Cancer Research, Sutton, UK

    M Greaves

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  1. V Enciso-Mora
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  2. F J Hosking
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  3. E Sheridan
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  4. S E Kinsey
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  5. T Lightfoot
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  7. J A E Irving
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  9. J M Allan
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  10. M Taylor
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  11. M Greaves
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  12. R S Houlston
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Correspondence to R S Houlston.

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Enciso-Mora, V., Hosking, F., Sheridan, E. et al. Common genetic variation contributes significantly to the risk of childhood B-cell precursor acute lymphoblastic leukemia. Leukemia 26, 2212–2215 (2012). https://doi.org/10.1038/leu.2012.89

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  • DOI: https://doi.org/10.1038/leu.2012.89

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