Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

Autor:	Law PJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Speedy HE; Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK., Camp NJ; Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA., Sava GP; Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK., Skibola CF; Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA., Holroyd A; Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK., Joseph V; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA., Sunter NJ; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Nieters A; Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg 79108, Germany., Bea S; Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic, Barcelona 08036, Spain., Monnereau A; Registre des hémopathies malignes de la Gironde, Institut Bergonié, Inserm U1219 EPICENE, 33076 Bordeaux, France.; Epidemiology of Childhood and Adolescent Cancers Group, Inserm, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité, Paris, F-94807, France.; Université Paris Descartes, Paris 75270, France., Martin-Garcia D; Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic, Barcelona 08036, Spain., Goldin LR; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Clot G; Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic, Barcelona 08036, Spain., Teras LR; Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA., Quintela I; Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado (CeGen-PRB2-ISCIII), CIBERER, 15782 Santiago de Compostela, Spain., Birmann BM; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA., Jayne S; Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester LE2 7LX, UK., Cozen W; Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.; Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA., Majid A; Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester LE2 7LX, UK., Smedby KE; Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Hematology Center, Karolinsak University Hospital, Stockholm 17176, Sweden., Lan Q; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Dearden C; The Royal Marsden NHS Foundation Trust, London SM2 5PT, UK., Brooks-Wilson AR; Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3.; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A1S6, Canada., Hall AG; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Purdue MP; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Mainou-Fowler T; Haematological Sciences, Medical School, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK., Vajdic CM; Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales 2052, Australia., Jackson GH; Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK., Cocco P; Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy., Marr H; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Zhang Y; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut 06520, USA., Zheng T; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut 06520, USA., Giles GG; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria 3010, Australia., Lawrence C; Westat, Rockville, Maryland 20850, USA., Call TG; Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA., Liebow M; Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA., Melbye M; Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen, Denmark.; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA., Glimelius B; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75105 Uppsala, Sweden., Mansouri L; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75105 Uppsala, Sweden., Glenn M; Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA., Curtin K; Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA., Diver WR; Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA., Link BK; Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA., Conde L; Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA., Bracci PM; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94118, USA., Holly EA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94118, USA., Jackson RD; Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, Ohio 43210, USA., Tinker LF; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA., Benavente Y; Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.; CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona 08036, Spain., Boffetta P; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA., Brennan P; International Agency for Research on Cancer, Lyon 69372, France., Maynadie M; Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France., McKay J; International Agency for Research on Cancer, Lyon 69372, France., Albanes D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Weinstein S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Wang Z; Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA., Caporaso NE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Morton LM; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Severson RK; Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan 48201, USA., Riboli E; School of Public Health, Imperial College London, London W2 1PG, UK., Vineis P; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.; Human Genetics Foundation, 10126 Turin, Italy., Vermeulen RC; Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3508 TD, The Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands., Southey MC; Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia., Milne RL; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria 3010, Australia., Clavel J; Epidemiology of Childhood and Adolescent Cancers Group, Inserm, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris F-94807, France.; Université Paris Descartes, 75270 Paris, France., Topka S; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA., Spinelli JJ; Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3.; School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z3., Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA., Ennas MG; Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari 09042, Italy., Summerfield G; Department of Haematology, Queen Elizabeth Hospital, Gateshead NE9 6SX, UK., Ferri GM; Interdisciplinary Department of Medicine, University of Bari, Bari 70124, Italy., Harris RJ; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3BX, UK., Miligi L; Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence 50139, Italy., Pettitt AR; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3BX, UK., North KE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.; Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA., Allsup DJ; Queens Centre for Haematology and Oncology, Castle Hill Hospital, Hull and East Yorkshire NHS Trust, Cottingham HU16 5JQ, UK., Fraumeni JF; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Bailey JR; Queens Centre for Haematology and Oncology, Castle Hill Hospital, Hull and East Yorkshire NHS Trust, Cottingham HU16 5JQ, UK., Offit K; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA., Pratt G; Department of Haematology, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK., Hjalgrim H; Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen, Denmark., Pepper C; Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK., Chanock SJ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Fegan C; Cardiff and Vale National Health Service Trust, Heath Park, Cardiff CF14 4XW, UK., Rosenquist R; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, 75105 Uppsala, Sweden., de Sanjose S; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.; International Agency for Research on Cancer, Lyon 69372, France., Carracedo A; Grupo de Medicina Xenomica, Universidade de Santiago de Compostela, Centro Nacional de Genotipado (CeGen-PRB2-ISCIII), CIBERER, 15782 Santiago de Compostela, Spain.; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, KSA., Dyer MJ; Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester LE2 7LX, UK., Catovsky D; Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK., Campo E; Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Hospital Clínic, Barcelona 08036, Spain.; Unitat de Hematología, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona 08036, Spain., Cerhan JR; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA., Allan JM; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK., Rothman N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA., Houlston R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK., Slager S; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2017 Feb 06; Vol. 8, pp. 14175. Date of Electronic Publication: 2017 Feb 06.
DOI:	10.1038/ncomms14175
Abstrakt:	Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10 -13 ), 1q42.13 (rs41271473, P=1.06 × 10 -10 ), 4q24 (rs71597109, P=1.37 × 10 -10 ), 4q35.1 (rs57214277, P=3.69 × 10 -8 ), 6p21.31 (rs3800461, P=1.97 × 10 -8 ), 11q23.2 (rs61904987, P=2.64 × 10 -11 ), 18q21.1 (rs1036935, P=3.27 × 10 -8 ), 19p13.3 (rs7254272, P=4.67 × 10 -8 ) and 22q13.33 (rs140522, P=2.70 × 10 -9 ). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response. Competing Interests: The authors declare no competing financial interests.
Databáze:	MEDLINE
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