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Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE)

Leukemia volume 26, pages 2561–2564 (2012)Cite this article

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Every year, acute lymphoblastic leukaemia (ALL) affects about 400 children aged <15 years in France,1 accounting for approximately 80% of the acute leukaemia (AL) cases. The heterogeneity of cell types is reflected in the heterogeneity of clinical presentation, prognosis and, possibly, risk factors. In addition to Down’s syndrome, a few inheritable predisposing diseases and high-dose ionizing radiations increase the risk of ALL. Some environmental, infectious and genetic factors2 are consistently suspected. The first ALL genome-wide association studies (GWAS) reported clear associations between ALL and single-nucleotide polymorphisms (SNPs) flanking the Ikaros family zinc finger 1 gene (IKZF1) in 7p12.2 (rs6964823, rs4132601, rs6944602(ref. 3) or rs11978267(ref. 4)), and the AT-rich interactive domain 5b gene (ARID5B) in 10q21.2 (rs7073837, rs10740055, rs7089424,3 or rs10821936, rs10994982(ref. 4). The latter association was more pronounced for hyperdiploid ALL in both GWAS. In the UK study, the SNP rs2239633 in the CCAAT/enhancer-binding protein epsilon gene (CEBPE) was also associated with ALL. Sherbone et al.5 analysed a subset of 34 SNPs selected in the UK GWAS3 and reported an association with rs3731217 in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. In addition, in a recent GWAS, four additional SNPs were associated with TEL-AML1-positive ALL (rs17505102 (TP63), rs1945213 (OR8U8), rs920590 (INTS10) and rs3942852 (PTPRJ)),6 requiring further investigation.

We report the results of a GWAS conducted on the ALL cases from the ESCALE (Etude Sur les Cancers et les Leucémies de l’Enfant) nationwide registry-based study and generic controls. In addition, the SNPs associated with AL in the previous GWAS were considered in the ESCALE case–control study.

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Acknowledgements

We are grateful to Claire Mulot, who was in charge of the biological collection at the Biological Resource Centre of Saints-Pères, INSERM U775; the CEPH and the Centre National de Génotypage, which genotyped the cases; and IntegraGen, which genotyped the controls. We also thank Florence Demenais and the UMR-946 unit (Inserm-Université Paris Diderot) and Fondation Jean Dausset-CEPH for their support. We also express our gratitude to Marie-Hélène Da Silva, Christophe Steffen and Florence Menegaux (INSERM U1018, Environmental Epidemiology of Cancer), who contributed to the recruitment of the cases; Aurélie Guyot-Goubin and the staff of the French National Registry of Childhood Blood Malignancies, who contributed to case detection and verification; and Sabine Mélèze and Marie-Anne Noel (Institut CSA), who coordinated the selection of the controls. We also thank all of the Société Française de lutte contre les Cancers de l’Enfant et de l’Adolescent (SFCE) principal investigators: André Baruchel (Hôpital Saint-Louis/Hôpital Robert Debré, Paris, France), Claire Berger (Centre Hospitalier Universitaire, Saint-Etienne, France), Christophe Bergeron (Centre Léon Bérard, Lyon, France), Jean-Louis Bernard (Hôpital La Timone, Marseille), Yves Bertrand (Hôpital Debrousse, Lyon, France), Pierre Bordigoni (Centre Hospitalier Universitaire, Nancy, France), Patrick Boutard (Centre Hospitalier Régional Universitaire, Caen, France), Gérard Couillault (Hôpital d’Enfants, Dijon, France), Christophe Piguet (Centre Hospitalier Régional Universitaire, Limoges, France), Anne-Sophie Defachelles (Centre Oscar Lambret, Lille, France), François Demeocq (Hôpital Hôtel-Dieu, Clermont-Ferrand, France), Alain Fischer (Hôpital des Enfants Malades, Paris, France), Virginie Gandemer (Centre Hospitalier Universitaire – Hôpital Sud, Rennes, France), Dominique Valteau-Couanet (Institut Gustave Roussy, Villejuif, France), Jean-Pierre Lamagnere (Centre Gatien de Clocheville, Tours, France), Françoise Lapierre (Centre Hospitalier Universitaire Jean Bernard, Poitiers, France), Guy Leverger (Hôpital Armand-Trousseau, Paris, France), Patrick Lutz (Hôpital de Hautepierre, Strasbourg, France), Geneviève Margueritte (Hôpital Arnaud de Villeneuve, Montpellier, France), Françoise Mechinaud (Hôpital Mère et Enfants, Nantes, France), Gérard Michel (Hôpital La Timone, Marseille, France), Frédéric Millot (Centre Hospitalier Universitaire Jean Bernard, Poitiers, France), Martine Münzer (American Memorial Hospital, Reims, France), Brigitte Nelken (Hôpital Jeanne de Flandre, Lille, France), Hélène Pacquement (Institut Curie, Paris, France), Brigitte Pautard (Centre Hospitalier Universitaire, Amiens, France), Yves Perel (Hôpital Pellegrin Tripode, Bordeaux, France), Alain Pierre-Kahn (Hôpital Enfants Malades, Paris, France), Emmanuel Plouvier (Centre Hospitalier Régional, Besançon, France), Xavier Rialland (Centre Hospitalier Universitaire, Angers, France), Alain Robert (Hôpital des Enfants, Toulouse), Hervé Rubie (Hôpital des Enfants, Toulouse, France), Nicolas Sirvent (L’Archet, Nice, France), Christine Soler (Fondation Lenval, Nice, France) and Jean-Pierre Vannier (Hôpital Charles Nicolle, Rouen, France). This work was supported by grants from INSERM, the Fondation de France, the Association pour la Recherche sur le Cancer (ARC), the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), the Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET), the association Cent pour sang la vie, the Institut National du Cancer (INCa), the Agence Nationale de la Recherche (ANR) and Cancéropôle Ile de France.

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Author notes

  1. L Orsi and J Rudant: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Environmental Epidemiology of Cancers, INSERM, U1018, Villejuif, France

    L Orsi, J Rudant, A Bonaventure, S Goujon-Bellec, D Hémon & J Clavel

  2. Department of Environmental Epidemiology of Cancers, Paris-Sud University, UMR-S1018, Research Center in Epidemiology and Population Health, Villejuif, France

    L Orsi, J Rudant, A Bonaventure, S Goujon-Bellec, D Hémon & J Clavel

  3. French National Registry of Childhood Blood Malignancies (RNHE), Villejuif, France

    J Rudant, S Goujon-Bellec & J Clavel

  4. Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France

    E Corda

  5. Inserm, Univ Paris Diderot, UMR-S-946, Genetic Variation and Human Diseases Unit, Paris, France

    E Corda

  6. School of Biomedical Sciences, Faculty of Health, University of Newcastle, Newcastle, NSW, Australia

    T-J Evans & R J Scott

  7. AP-HP, Hôpital Armand Trousseau, Paris, France

    A Petit

  8. Université Paris 6 Pierre et Marie Curie, Paris, France

    A Petit

  9. Institut d’Hémato-Oncologie Pédiatrique, Lyon, France

    Y Bertrand

  10. Pôle Enfant, CHRU, Lille, France

    B Nelken

  11. Université Lille Nord de France, Lille, France

    B Nelken

  12. Hôpital des Enfants, Toulouse, France

    A Robert

  13. AP-HM, Hôpital la Timone, Marseille, France

    G Michel

  14. Hôpital Arnaud de Villeneuve, Montpellier, France

    N Sirvent

  15. Hôpital d’enfants, CHU de Nancy, Vandoeuvre, France

    P Chastagner

  16. Hôpital Pellegrin Tripode, Bordeaux, France

    S Ducassou

  17. Hôpital Mère-Enfant, CHU-Nantes, Nantes, France

    X Rialland

  18. CHU d’Angers, Angers, France

    X Rialland

  19. Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Crawley, WA, Australia

    E Milne

  20. AP-HP, Hôpital Robert Debré, Paris, France

    A Baruchel

  21. Université Paris 7 Denis Diderot, Paris, France

    A Baruchel

Authors
  1. L Orsi
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  2. J Rudant
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  3. A Bonaventure
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  4. S Goujon-Bellec
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  5. E Corda
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  6. T-J Evans
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  7. A Petit
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  8. Y Bertrand
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  9. B Nelken
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  10. A Robert
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  11. G Michel
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  12. N Sirvent
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  14. S Ducassou
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  15. X Rialland
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  16. D Hémon
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  17. E Milne
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  18. R J Scott
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  19. A Baruchel
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  20. J Clavel
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Corresponding author

Correspondence to J Clavel.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Leukemia website

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Orsi, L., Rudant, J., Bonaventure, A. et al. Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE). Leukemia 26, 2561–2564 (2012). https://doi.org/10.1038/leu.2012.148

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