Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk
Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences a...
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| Published in | Nature genetics Vol. 42; no. 6; pp. 492 - 494 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.06.2010
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 × 10−11), irrespective of cell lineage. |
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| AbstractList | To search for additional new variants influencing the risk of ALL, we have performed replication of 34 SNPs selected on the basis of statistical significance (P < 0.0001) coupled with considerations of minor allele frequency > 0.05, Hardy-Weinberg equilibrium (P > 0.05 in controls) and potential candidacy of nearby genes (on the basis of a role in B-cell and/or cancer biology) (Supplementary Table 1) in additional case-control series. R.S.H. drafted the manuscript with contributions from F.J.H., A.L.S. and M.G.; A.L.S. performed overall project management, development, database development and oversaw laboratory analyses; F.J.H. performed statistical analyses; F.J.H. and A.L.S. performed bioinformatics analyses; J.V. and E.P. performed UK sample preparation and genotyping; E.S. and S.E.K. performed curation and sample preparation of the Medical Research Council ALL 97 trial samples; T.L. and E.R. managed and maintained UKCCS sample data; M.T. performed curation and sample preparation of United Kingdom Childhood Cancer Study samples; J.M.A. and J.A.E.I. performed ascertainment, curation and sample preparation of the Northern Institute for Cancer Research case series. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A ) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 × 10 −11 ), irrespective of cell lineage. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 x 10(-11)), irrespective of cell lineage. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 10 super(-11)), irrespective of cell lineage. Richard Houlston and colleagues report a new risk locus for childhood acute lymphoblastic leukemia. The associated variant is located in the CDKN2A gene at chromosome 9p21. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A ) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 × 10 −11 ), irrespective of cell lineage. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 × 10−11), irrespective of cell lineage. Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 x [10.sup.-11]), irrespective of cell lineage. |
| Audience | Academic |
| Author | Prasad, Rashmi B Ogawa, Seishi Sheridan, Eamonn Allan, James M Hemminki, Kari Houlston, Richard S Stanulla, Martin Dobbins, Sara E Neira, Anna Gonzalez Kumar, Rajiv Richards, Sue Koeffler, H Phillip Sherborne, Amy L Krajinovic, Maja Kawamata, Norihiko Lightfoot, Tracey Taylor, Malcolm Irving, Julie A E Tomlinson, Ian P Semsei, Ágnes F Healy, Jasmine Gast, Andreas Harrison, Christine J Greaves, Mel Szalai, Csaba Kinsey, Sally E Koehler, Rolf Papaemmanuil, Elli Ma, Yussanne Schrappe, Martin Erdelyi, Daniel J Vijayakrishnan, Jayaram Sinnett, Daniel Moorman, Anthony V Bartram, Claus R Hosking, Fay J Zimmermann, Martin Roman, Eve |
| AuthorAffiliation | 15 Spanish National Cancer Research Center (CNIO), Madrid, Spain 9 Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK 14 Division of Hematology-Oncology, Research Center of the Sainte-Justine University Health Center, University of Montréal, Montréal, Quebec, Canada 4 Department of Pediatrics, Acute Lymphoblastic Leukemia–Berlin-Frankfurt-Munster (ALL-BFM) Clinical Trial Center, University of Kiel, Kiel, Germany 19 Section of Haemato-oncology, Institute of Cancer Research, Sutton, Surrey, UK 18 National University of Singapore Institute of Human Genetics, Singapore, Singapore 5 Yorkshire Regional Genetic Service, St. James’s University Hospital, Leeds, UK 12 Department of Pediatric Hematology and Oncology, Medical School, Hannover, Germany 6 Cancer Immunogenetics Group, School of Cancer Sciences, University of Manchester, Research Floor, St. Mary’s Hospital, Manchester, UK 16 Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of Calif |
| AuthorAffiliation_xml | – name: 16 Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California, USA – name: 18 National University of Singapore Institute of Human Genetics, Singapore, Singapore – name: 1 Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK – name: 13 Department of Genetic, Cell- and Immunobiology, SNP Core Facility Laboratorium, Semmelweis University, Budapest, Hungary – name: 12 Department of Pediatric Hematology and Oncology, Medical School, Hannover, Germany – name: 19 Section of Haemato-oncology, Institute of Cancer Research, Sutton, Surrey, UK – name: 5 Yorkshire Regional Genetic Service, St. James’s University Hospital, Leeds, UK – name: 2 Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany – name: 3 Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany – name: 10 Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics, Oxford, UK – name: 6 Cancer Immunogenetics Group, School of Cancer Sciences, University of Manchester, Research Floor, St. Mary’s Hospital, Manchester, UK – name: 17 Regeneration Medicine of Hematopoiesis, University of Tokyo, School of Medicine, Tokyo, Japan – name: 9 Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK – name: 4 Department of Pediatrics, Acute Lymphoblastic Leukemia–Berlin-Frankfurt-Munster (ALL-BFM) Clinical Trial Center, University of Kiel, Kiel, Germany – name: 8 Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, UK – name: 14 Division of Hematology-Oncology, Research Center of the Sainte-Justine University Health Center, University of Montréal, Montréal, Quebec, Canada – name: 15 Spanish National Cancer Research Center (CNIO), Madrid, Spain – name: 11 Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, UK – name: 7 Department of Paediatric and Adolescent Oncology and Haematology, St. James’s University Hospital, Leeds, UK |
| Author_xml | – givenname: Andreas surname: Gast fullname: Gast, Andreas organization: Division of Molecular Genetic Epidemiology, German Cancer Research Centre – givenname: Sally E surname: Kinsey fullname: Kinsey, Sally E organization: Department of Paediatric and Adolescent Oncology and Haematology, St. James's University Hospital – givenname: Eve surname: Roman fullname: Roman, Eve organization: Epidemiology and Genetics Unit, Department of Health Sciences, University of York – givenname: Martin surname: Schrappe fullname: Schrappe, Martin organization: Department of Pediatrics, Acute Lymphoblastic Leukemia-Berlin-Frankfurt-Munster (ALL-BFM) Clinical Trial Center, University of Kiel – givenname: H Phillip surname: Koeffler fullname: Koeffler, H Phillip organization: National University of Singapore Institute of Human Genetics – givenname: Fay J surname: Hosking fullname: Hosking, Fay J organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Martin surname: Stanulla fullname: Stanulla, Martin organization: Department of Pediatrics, Acute Lymphoblastic Leukemia-Berlin-Frankfurt-Munster (ALL-BFM) Clinical Trial Center, University of Kiel – givenname: Daniel surname: Sinnett fullname: Sinnett, Daniel organization: Division of Hematology-Oncology, Research Center of the Sainte-Justine University Health Center, University of Montréal – givenname: Christine J surname: Harrison fullname: Harrison, Christine J organization: Northern Institute for Cancer Research, Newcastle University – givenname: Jayaram surname: Vijayakrishnan fullname: Vijayakrishnan, Jayaram organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Sara E surname: Dobbins fullname: Dobbins, Sara E organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Richard S surname: Houlston fullname: Houlston, Richard S organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Martin surname: Zimmermann fullname: Zimmermann, Martin organization: Department of Pediatric Hematology and Oncology, Medical School – givenname: Daniel J surname: Erdelyi fullname: Erdelyi, Daniel J organization: Department of Genetic, Cell- and Immunobiology, SNP Core Facility Laboratorium, Semmelweis University, Budapest – givenname: Claus R surname: Bartram fullname: Bartram, Claus R organization: Institute of Human Genetics, University of Heidelberg – givenname: Sue surname: Richards fullname: Richards, Sue organization: Clinical Trial Service Unit and Epidemiological Studies Unit – givenname: Anna Gonzalez surname: Neira fullname: Neira, Anna Gonzalez organization: Spanish National Cancer Research Center (CNIO) – givenname: Seishi surname: Ogawa fullname: Ogawa, Seishi organization: Regeneration Medicine of Hematopoiesis, University of Tokyo, School of Medicine – givenname: Jasmine surname: Healy fullname: Healy, Jasmine organization: Division of Hematology-Oncology, Research Center of the Sainte-Justine University Health Center, University of Montréal – givenname: Kari surname: Hemminki fullname: Hemminki, Kari organization: Division of Molecular Genetic Epidemiology, German Cancer Research Centre – givenname: Elli surname: Papaemmanuil fullname: Papaemmanuil, Elli organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Norihiko surname: Kawamata fullname: Kawamata, Norihiko organization: Division of Hematology and Oncology, Cedars-Sinai Medical Center, University of California Los Angeles School of Medicine – givenname: Ágnes F surname: Semsei fullname: Semsei, Ágnes F organization: Department of Genetic, Cell- and Immunobiology, SNP Core Facility Laboratorium, Semmelweis University, Budapest – givenname: Julie A E surname: Irving fullname: Irving, Julie A E organization: Northern Institute for Cancer Research, Newcastle University – givenname: Amy L surname: Sherborne fullname: Sherborne, Amy L organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Rajiv surname: Kumar fullname: Kumar, Rajiv organization: Division of Molecular Genetic Epidemiology, German Cancer Research Centre – givenname: Yussanne surname: Ma fullname: Ma, Yussanne organization: Section of Cancer Genetics, Institute of Cancer Research – givenname: Anthony V surname: Moorman fullname: Moorman, Anthony V organization: Northern Institute for Cancer Research, Newcastle University – givenname: Mel surname: Greaves fullname: Greaves, Mel organization: Section of Haemato-oncology, Institute of Cancer Research – givenname: Tracey surname: Lightfoot fullname: Lightfoot, Tracey organization: Epidemiology and Genetics Unit, Department of Health Sciences, University of York – givenname: Rolf surname: Koehler fullname: Koehler, Rolf organization: Institute of Human Genetics, University of Heidelberg – givenname: Rashmi B surname: Prasad fullname: Prasad, Rashmi B organization: Division of Molecular Genetic Epidemiology, German Cancer Research Centre – givenname: Malcolm surname: Taylor fullname: Taylor, Malcolm organization: Cancer Immunogenetics Group, School of Cancer Sciences, University of Manchester, Research Floor, St. Mary's Hospital – givenname: Csaba surname: Szalai fullname: Szalai, Csaba organization: Department of Genetic, Cell- and Immunobiology, SNP Core Facility Laboratorium, Semmelweis University, Budapest – givenname: Eamonn surname: Sheridan fullname: Sheridan, Eamonn organization: Yorkshire Regional Genetic Service, St. James's University Hospital – givenname: James M surname: Allan fullname: Allan, James M organization: Northern Institute for Cancer Research, Newcastle University – givenname: Ian P surname: Tomlinson fullname: Tomlinson, Ian P organization: Molecular and Population Genetics, Wellcome Trust Centre for Human Genetics – givenname: Maja surname: Krajinovic fullname: Krajinovic, Maja organization: Division of Hematology-Oncology, Research Center of the Sainte-Justine University Health Center, University of Montréal |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22858045$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/20453839$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Springer Nature America, Inc. 2010 2015 INIST-CNRS COPYRIGHT 2010 Nature Publishing Group Copyright Nature Publishing Group Jun 2010 2010 Nature America, Inc. All rights reserved. 2010 |
| Copyright_xml | – notice: Springer Nature America, Inc. 2010 – notice: 2015 INIST-CNRS – notice: COPYRIGHT 2010 Nature Publishing Group – notice: Copyright Nature Publishing Group Jun 2010 – notice: 2010 Nature America, Inc. All rights reserved. 2010 |
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| DOI | 10.1038/ng.585 |
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| References | Shete, S. (b8) 2009; 41 Bishop, D.T. (b6) 2009; 41 Sulong, S. (b11) 2009; 113 Treviño, L.R. (b2) 2009; 41 Mirebeau, D. (b12) 2006; 91 Iacobucci, I. (b15) 2010; 24 Mullighan, C.G., Downing, J.R. (b3) 2009; 23 Stacey, S.N. (b7) 2009; 41 Bateman, C. (b4) Papaemmanuil, E. (b1) 2009; 41 Falchi, M. (b5) 2009; 41 Stranger, B.E. (b13) 2005; 1 Scott, L.J. (b9) 2007; 316 McPherson, R. (b10) 2007; 316 Kitagawa, Y. (b14) 2002; 277 PapaemmanuilENat. Genet.20094110061010 Bateman, C. et al. Blood published online. doi:10.1182/blood-2009-10-25143 (8 January 2010). StaceySNNat. Genet.200941909914 ScottLJScience200731613411345 IacobucciILeukemia2010246673 McPhersonRScience200731614881491 TreviñoLRNat. Genet.20094110011005 KitagawaYJ. Biol. Chem.20022774628946297 MullighanCGDowningJRLeukemia20092312091218 BishopDTNat. Genet.200941920925 MirebeauDHaematologica200691881885 FalchiMNat. Genet.200941915919 StrangerBEPLoS Genet.20051e78 SulongSBlood2009113100107 SheteSNat. Genet.200941899904 M Falchi (BFng585_CR5) 2009; 41 BFng585_CR4 D Mirebeau (BFng585_CR12) 2006; 91 CG Mullighan (BFng585_CR3) 2009; 23 R McPherson (BFng585_CR10) 2007; 316 BE Stranger (BFng585_CR13) 2005; 1 LJ Scott (BFng585_CR9) 2007; 316 DT Bishop (BFng585_CR6) 2009; 41 E Papaemmanuil (BFng585_CR1) 2009; 41 I Iacobucci (BFng585_CR15) 2010; 24 SN Stacey (BFng585_CR7) 2009; 41 S Sulong (BFng585_CR11) 2009; 113 S Shete (BFng585_CR8) 2009; 41 Y Kitagawa (BFng585_CR14) 2002; 277 LR Treviño (BFng585_CR2) 2009; 41 |
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| Snippet | Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation... Richard Houlston and colleagues report a new risk locus for childhood acute lymphoblastic leukemia. The associated variant is located in the CDKN2A gene at... To search for additional new variants influencing the risk of ALL, we have performed replication of 34 SNPs selected on the basis of statistical significance... |
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| SubjectTerms | 631/208/726/649 692/699/67/1990/283/2125 692/699/67/69 Acute lymphocytic leukemia Agriculture Animal Genetics and Genomics Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedicine brief-communication Cancer Research Case-Control Studies Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Children Chromosomes, Human, Pair 9 Colorectal cancer Data collection Diagnosis Fundamental and applied biological sciences. Psychology Gene Function Genes, p16 Genetic aspects Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genotype & phenotype Haplotypes Health aspects Hematologic and hematopoietic diseases Hospitals Human Genetics Humans Leukemia Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical research Medical sciences Molecular and cellular biology Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Project management Risk factors Sample preparation Single nucleotide polymorphisms Statistical analysis Studies |
| Title | Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk |
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