Association analyses identify 31 new risk loci for colorectal cancer susceptibility View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-05-14

AUTHORS

Philip J. Law, Maria Timofeeva, Ceres Fernandez-Rozadilla, Peter Broderick, James Studd, Juan Fernandez-Tajes, Susan Farrington, Victoria Svinti, Claire Palles, Giulia Orlando, Amit Sud, Amy Holroyd, Steven Penegar, Evropi Theodoratou, Peter Vaughan-Shaw, Harry Campbell, Lina Zgaga, Caroline Hayward, Archie Campbell, Sarah Harris, Ian J. Deary, John Starr, Laura Gatcombe, Maria Pinna, Sarah Briggs, Lynn Martin, Emma Jaeger, Archana Sharma-Oates, James East, Simon Leedham, Roland Arnold, Elaine Johnstone, Haitao Wang, David Kerr, Rachel Kerr, Tim Maughan, Richard Kaplan, Nada Al-Tassan, Kimmo Palin, Ulrika A. Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti-Pekka Sarin, Johan G. Eriksson, Harri Rissanen, Paul Knekt, Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Daniel D. Buchanan, Aung-Ko Win, John Hopper, Mark E. Jenkins, Noralane M. Lindor, Polly A. Newcomb, Steven Gallinger, David Duggan, Graham Casey, Per Hoffmann, Markus M. Nöthen, Karl-Heinz Jöckel, Douglas F. Easton, Paul D. P. Pharoah, Julian Peto, Federico Canzian, Anthony Swerdlow, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Nora Pashayan, Andrea Harkin, Karen Allan, John McQueen, James Paul, Timothy Iveson, Mark Saunders, Katja Butterbach, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Iva Kirac, Petar Matošević, Philipp Hofer, Stefanie Brezina, Andrea Gsur, Jeremy P. Cheadle, Lauri A. Aaltonen, Ian Tomlinson, Richard S. Houlston, Malcolm G. Dunlop

ABSTRACT

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention. More... »

PAGES

2154

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    10

    Author Affiliations

  • Division of Genetics and Epidemiology, The Institute of Cancer Research, SW7 3RP, London, UK
  • Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, EH4 2XU, Edinburgh, UK
  • Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, B15 2TT, Birmingham, UK
  • Wellcome Centre for Human Genetics, McCarthy Group, Roosevelt Drive, OX3 7BN, Oxford, UK
  • Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, B15 2TT, Edgbaston, Birmingham, UK
  • Centre for Global Health Research, Usher Institute, University of Edinburgh, EH8 9AG, Edinburgh, UK
  • Department of Public Health and Primary Care, Institute of Population Health, Trinity College Dublin, University of Dublin, D02 PN40, Dublin, Ireland
  • Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, EH4 2XU, Edinburgh, UK
  • Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU, Edinburgh, UK
  • Department of Psychology, University of Edinburgh, EH8 9JZ, Edinburgh, UK
  • Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, EH8 9JZ, Edinburgh, UK
  • Alzheimer Scotland Dementia Research Centre, University of Edinburgh, EH8 9JZ, Edinburgh, UK
  • Translational Gastroenterology Unit, Nuffield Department. of Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DU, Oxford, UK
  • Cancer Bioinfomatics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, B15 2TT, Birmingham, UK
  • Department of Oncology, University of Oxford, Old Road Campus Research Building, OX3 7LE, Oxford, UK
  • Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, OX3 9DU, Oxford, UK
  • Medical Research Council Clinical Trials Unit, Aviation House, 125 Kingsway, WC2B 6NH, London, UK
  • Department of Genetics, King Faisal Specialist Hospital and Research Center, 11211, Riyadh, Saudi Arabia
  • Department of Medical and Clinical Genetics, Medicum and Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, 00014, Helsinki, Finland
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014, Helsinki, Finland
  • Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, 00014, Helsinki, Finland
  • National Institute for Health and Welfare, 00271, Helsinki, Finland
  • Faculty of Social Sciences, University of Tampere, 33014, Tampere, Finland
  • Broad Institute of MIT and Harvard, 02142, Cambridge, MA, USA
  • Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, 02114, Boston, MA, USA
  • Department of Surgery, Abdominal Center, Helsinki University Hospital, 00029, Helsinki, Finland
  • Department of Pathology, Central Finland Central Hospital, 40620, Jyväskylä, Finland
  • Department of Health Sciences, Faculty of Sport and Health Sciences, University of Jyväskylä, 40014, Jyväskylä, Finland
  • Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, 3010, Parkville, VIC, Australia
  • Centre for Epidemiology and Biostatistics, The University of Melbourne, 3010, Melbourne, VIC, Australia
  • Department of Health Sciences Research, Mayo Clinic, 85259, Scottsdale, AZ, USA
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA, USA
  • Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, ON M5G 1X5, Toronto, Canada
  • Translational Genomics Research Institute (TGen), An Affiliate of City of Hope, 85004, Phoenix, AZ, USA
  • Center for Public Health Genomics, University of Virginia, 22903, Virginia, VA, USA
  • Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany
  • Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, 53127, Bonn, Germany
  • Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany
  • Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, Cambridge, UK
  • Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, WC1E 7HT, London, UK
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
  • Division of Breast Cancer Research, The Institute of Cancer Research, SW3 6JB, London, UK
  • Royal Marsden NHS Foundation Trust, SW3 6JJ, London, UK
  • Warwick Medical School, University of Warwick, CV4 7HL, Coventry, UK
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, CB1 8RN, Cambridge, UK
  • Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, G61 1BD, Glasgow, UK
  • University Hospital Southampton NHS Foundation Trust, SO16 6YD, Southampton, UK
  • The Christie NHS Foundation Trust, M20 4BX, Manchester, UK
  • Division of Clinical Epidemiology and Aging Research, Deutsches Krebsforschungszentrum, 69120, Heidelberg, Germany
  • University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany
  • Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany
  • Department of Surgical Oncology, University Hospital for Tumours, Sestre milosrdnice University Hospital Centre, 10000, Zagreb, Croatia
  • Department of Surgery, University Hospital Center Zagreb, 10000, Zagreb, Croatia
  • Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria
  • Division of Cancer and Genetics, School of Medicine, Cardiff University, CF14 4XN, Cardiff, UK
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09775-w

    DOI

    http://dx.doi.org/10.1038/s41467-019-09775-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1114225749

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31089142


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