Genome-wide Association Study Identifies Multiple Risk Loci for Chronic Lymphocytic Leukemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-06-16

AUTHORS

Sonja I. Berndt, Christine F. Skibola, Vijai Joseph, Nicola J. Camp, Alexandra Nieters, Zhaoming Wang, Wendy Cozen, Alain Monnereau, Sophia S. Wang, Rachel S. Kelly, Qing Lan, Lauren R. Teras, Nilanjan Chatterjee, Charles C. Chung, Meredith Yeager, Angela R. Brooks-Wilson, Patricia Hartge, Mark P. Purdue, Brenda M. Birmann, Bruce K. Armstrong, Pierluigi Cocco, Yawei Zhang, Gianluca Severi, Anne Zeleniuch-Jacquotte, Charles Lawrence, Laurie Burdette, Jeffrey Yuenger, Amy Hutchinson, Kevin B. Jacobs, Timothy G. Call, Tait D. Shanafelt, Anne J. Novak, Neil E. Kay, Mark Liebow, Alice H. Wang, Karin E Smedby, Hans-Olov Adami, Mads Melbye, Bengt Glimelius, Ellen T. Chang, Martha Glenn, Karen Curtin, Lisa A. Cannon-Albright, Brandt Jones, W. Ryan Diver, Brian K. Link, George J. Weiner, Lucia Conde, Paige M. Bracci, Jacques Riby, Elizabeth A. Holly, Martyn T. Smith, Rebecca D. Jackson, Lesley F. Tinker, Yolanda Benavente, Nikolaus Becker, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, James McKay, Anthony Staines, Kari G. Rabe, Sara J. Achenbach, Celine M. Vachon, Lynn R Goldin, Sara S. Strom, Mark C. Lanasa, Logan G. Spector, Jose F. Leis, Julie M. Cunningham, J. Brice Weinberg, Vicki A. Morrison, Neil E. Caporaso, Aaron D. Norman, Martha S. Linet, Anneclaire J. De Roos, Lindsay M. Morton, Richard K. Severson, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Dimitrios Trichopoulos, Giovanna Masala, Elisabete Weiderpass, María-Dolores Chirlaque, Roel C H Vermeulen, Ruth C. Travis, Graham G. Giles, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Jacqueline Clavel, Tongzhang Zheng, Theodore R Holford, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, John J. Spinelli, Kimberly A. Bertrand, Francine Laden, Edward Giovannucci, Peter Kraft, Anne Kricker, Jenny Turner, Claire M. Vajdic, Maria Grazia Ennas, Giovanni M. Ferri, Lucia Miligi, Liming Liang, Joshua Sampson, Simon Crouch, Ju-hyun Park, Kari E. North, Angela Cox, John A. Snowden, Josh Wright, Angel Carracedo, Carlos Lopez-Otin, Silvia Bea, Itziar Salaverria, David Martin, Elias Campo, Joseph F. Fraumeni, Silvia de Sanjose, Henrik Hjalgrim, James R. Cerhan, Stephen J. Chanock, Nathaniel Rothman, Susan L. Slager

ABSTRACT

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism. More... »

PAGES

868-876

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    8

    VOLUME

    45

    Author Affiliations

  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  • School of Public Health, University of Alabama, Birmingham, Alabama, USA
  • Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
  • Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Hesse, Germany
  • Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  • Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  • Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex, France
  • Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California, USA
  • MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA
  • Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
  • Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
  • Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, Italy
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA
  • Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, Australia
  • Department of Population Health, New York University School of Medicine, New York, New York, USA
  • Health Studies Sector, Westat, Rockville, Maryland, USA
  • Division of Hematology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  • Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  • Division of General Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  • Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  • Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  • Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
  • Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden
  • Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA
  • Department of Internal Medicine, Huntsman Cancer Institute, Salt Lake City, Utah, USA
  • George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, USA
  • Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA
  • Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA
  • Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USA
  • Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio, USA
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  • Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
  • The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
  • Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon, France
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • EA 4184, Registre des Hémopathies Malignes de Côte d’Or, University of Burgundy and Dijon University Hospital, Dijon, France
  • Genetic Cancer susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon, France
  • School of Nursing and Human Sciences, Dublin City University, Dublin, Leinster, Ireland
  • Department of Epidemiology, M.D. Anderson Cancer Center, Houston, Texas, USA
  • Department of Medicine, Duke University and VA Medical Centers, Durham, North Carolina, USA
  • Division of Epidemiology/Clinical Research, University of Minnesota, Minneapolis, Minnesota, USA
  • Division of Hematology/Oncology, College of Medicine, Mayo Clinic, Phoenix, Arizona, USA
  • Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  • Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota, USA
  • Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA
  • School of Public Health, Imperial College London, London, United Kingdom
  • Human Genetics Foundation, Turin, Italy
  • Hellenic Health Foundation, Athens, Greece
  • Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy
  • Folkhalsan Research Center, Samfundet Folkhalsan, Helsinki, Finland
  • Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain
  • Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
  • Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
  • Department of Chronic Disease and Prevention, National Institute for Health and Welfare, Helsinki, Finland
  • U1018 EQ6, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif Cedex, France
  • Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA
  • Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada
  • Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
  • Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
  • Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
  • Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, New South Wales, Australia
  • Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
  • Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari, Italy
  • Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
  • Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy
  • Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, United Kingdom
  • Dongguk University-Seoul, Seoul, South Korea
  • Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
  • Department of Oncology, University of Sheffield, Sheffield, UK
  • Department of Oncology, University of Sheffield and Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  • Genomic Medicine Group CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain
  • Department of Biochemistry and Molecular Biology, Institute of Oncology, University of Oviedo, Oviedo, Spain
  • August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2652

    DOI

    http://dx.doi.org/10.1038/ng.2652

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031396611

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23770605


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