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A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1.
Vijayakrishnan, J; Kumar, R; Henrion, M Y R; Moorman, A V; Rachakonda, P S; Hosen, I; da Silva Filho, M I; Holroyd, A; Dobbins, S E; Koehler, R; Thomsen, H; Irving, J A; Allan, J M; Lightfoot, T; Roman, E; Kinsey, S E; Sheridan, E; Thompson, P D; Hoffmann, P; Nöthen, M M; Heilmann-Heimbach, S; Jöckel, K H; Greaves, M; Harrison, C J; Bartram, C R; Schrappe, M; Stanulla, M; Hemminki, K; Houlston, R S.
Affiliation
  • Vijayakrishnan J; Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK.
  • Kumar R; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • Henrion MY; Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK.
  • Moorman AV; Leukemia Research Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
  • Rachakonda PS; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • Hosen I; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • da Silva Filho MI; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • Holroyd A; Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK.
  • Dobbins SE; Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK.
  • Koehler R; Department of Human Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
  • Thomsen H; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
  • Irving JA; Leukemia Research Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
  • Allan JM; Leukemia Research Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
  • Lightfoot T; Department of Health Sciences, Epidemiology and Cancer Statistics Group, University of York, York, UK.
  • Roman E; Department of Health Sciences, Epidemiology and Cancer Statistics Group, University of York, York, UK.
  • Kinsey SE; Department of Paediatric and Adolescent Haematology and Oncology, Leeds General Infirmary, Leeds, UK.
  • Sheridan E; Medical Genetics Research Group, Leeds Institute of Biomedical & Clinical Sciences, University of Leeds, Leeds, UK.
  • Thompson PD; Paediatric and Familial Cancer Research Group, Institute of Cancer Sciences, University of Manchester, St Mary's Hospital, Manchester, UK.
  • Hoffmann P; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Nöthen MM; Department of Biomedicine, Human Genomics Research Group, University Hospital Basel, Basel, Switzerland.
  • Heilmann-Heimbach S; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Jöckel KH; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Greaves M; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany.
  • Harrison CJ; Haemato-Oncology Research Unit, Division of Molecular Pathology, Institute of Cancer Research, Sutton, UK.
  • Bartram CR; Leukemia Research Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
  • Schrappe M; Department of Human Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
  • Stanulla M; General Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
  • Hemminki K; Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany.
  • Houlston RS; Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
Leukemia ; 31(3): 573-579, 2017 03.
Article in En | MEDLINE | ID: mdl-27694927
ABSTRACT
Genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of childhood acute lymphoblastic leukemia (ALL). To identify new susceptibility loci for the largest subtype of ALL, B-cell precursor ALL (BCP-ALL), we conducted a meta-analysis of two GWASs with imputation using 1000 Genomes and UK10K Project data as reference (totaling 1658 cases and 7224 controls). After genotyping an additional 2525 cases and 3575 controls, we identify new susceptibility loci for BCP-ALL mapping to 10q26.13 (rs35837782, LHPP, P=1.38 × 10-11) and 12q23.1 (rs4762284, ELK3, P=8.41 × 10-9). We also provide confirmatory evidence for the existence of independent risk loci at 9p21.3, but show that the association marked by rs77728904 can be accounted for by linkage disequilibrium with the rare high-impact CDKN2A p.Ala148Thr variant rs3731249. Our data provide further insights into genetic susceptibility to ALL and its biology.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromosomes, Human, Pair 10 / Chromosomes, Human, Pair 12 / Genetic Predisposition to Disease / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Genetic Loci Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Leukemia Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2017 Document type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromosomes, Human, Pair 10 / Chromosomes, Human, Pair 12 / Genetic Predisposition to Disease / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Genetic Loci Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Child / Child, preschool / Female / Humans / Infant / Male Language: En Journal: Leukemia Journal subject: HEMATOLOGIA / NEOPLASIAS Year: 2017 Document type: Article Affiliation country: United kingdom