Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Author: Dunlop, Malcolm G; Dobbins, Sara E; Farrington, Susan M; Jones, Angela M; Palles, Claire; Whiffin, Nicola; Tenesa, Albert; Spain, Sarah; Broderick, Peter; Ooi, Li-Yin; Domingo, Enric; Smillie, Claire; Henrion, Marc; Frampton, Matthew; Martin, Lynn; Grimes, Graeme; Gorman, Maggie; Semple, Colin; Ma, Yusanne P; Barclay, Ella; Prendergast, James; Cazier, Jean-Baptiste; Olver, Bianca; Penegar, Steven; Lubbe, Steven; Chandler, Ian; Carvajal-Carmona, Luis G; Ballereau, Stephane; Lloyd, Amy; Vijayakrishnan, Jayaram; Zgaga, Lina; Rudan, Igor; Theodoratou, Evropi; Colorectal Tumour Gene Identification (CORGI) Consortium; Starr, John M; Deary, Ian; Kirac, Iva; Kovacevic, Dujo; Aaltonen, Lauri A; Renkonen-Sinisalo, Laura; Mecklin, Jukka-Pekka; Matsuda, Koichi; Nakamura, Yusuke; Okada, Yukinori; Gallinger, Steven; Duggan, David J; Conti, David; Newcomb, Polly A; Hopper, John L; Jenkins, Mark A; Schumacher, Fredrick; Casey, Graham; Easton, Douglas; Shah, Mitul; Pharoah, Paul; Lindblom, Annika; Liu, Tao; Swedish Low-Risk Colorectal Cancer Study Group; Smith, Christopher G; West, Hannah; Cheadle, Jeremy P; COIN Collaborative Group; Midgley, Rachel; Kerr, David J; Campbell, Harry; Tomlinson, Ian; Houlston, Richard S
Department: Inst för molekylär medicin och kirurgi / Dept of Molecular Medicine and Surgery
View/Open:  Author Accepted Manuscript (1.426Mb)  
Abstract
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.
URI: http://hdl.handle.net/10616/41405
Institution:
  • MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK
  • Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK
  • Wellcome Trust Centre for Human Genetics, Oxford, UK
  • Department of Histopathology, Royal Devon and Exeter Hospital, Exeter, UK
  • Public Health Sciences, University of Edinburgh, Edinburgh, UK
  • Department of Psychology, University of Edinburgh, Edinburgh, UK
  • Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Department of Surgical Oncology, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
  • Department of Surgery, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
  • Department of Medical Genetics, University of Helsinki, Helsinki, Finland
  • Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
  • Jyväskylä Central Hospital, University of Eastern Finland, Jyväskylä, Finland
  • Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
  • Laboratory for Statistical Analysis, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan
  • Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  • Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA
  • Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia
  • Department of Oncology, University of Cambridge, Cambridge, UK
  • Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK
  • Department of Oncology, Oxford University, Radcliffe Infirmary, Headington, Oxford, UK
  • Oxford NIHR Comprehensive Biomedical Research Centre, Oxford, UK
  • Family Cancer Clinic, St Mark's Hospital, Harrow and Imperial College, London, UK
  • Department of Clinical Genetics, University of Birmingham, Birmingham, UK
  • Department of Clinical Genetics, University of Manchester, Manchester, UK
  • Institutionen för Kliniska Vetenskaper, Danderyds Sjukhus, Karolinska Institutet, Stockholm, Sweden
  • Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden

Citation: Nat Genet. 2012 May 27;44(7):770-6.
Citation DOI: 10.1038/ng.2293
Citation PMID: 22634755
Citation ISI: 000305886900010
Publishing journal: Nature Genetics
Eprint status: Peer Reviewed
Version: Accepted
Issue date: 2013-02-07
Sponsorship:
  • Cancer Research UK
  • EU's Seventh Research Framework Programme (FP7)
  • Wellcome Trust
  • Juvenile Diabetes Research Foundation
  • National Institute for Health and Care Research
  • National Institute for Social Care and Health Research
  • Leukaemia Lymphoma Research Fund
  • Core Charity
  • Medical Research Council
  • Biotechnology and Biological Sciences Research Council
  • Royal Society
  • Chief Scientist Office of the Scottish Government
  • Lifelong Health and Wellbeing Initiative
  • Engineering and Physical Sciences Research Council
  • Economic and Social Research Council
  • Swedish Cancer Society
  • Swedish Research Council
  • Stockholm Cancer Foundation
  • Academy of Finland
  • Finnish Cancer Society
  • Sigrid Juselius Foundation
  • NIH National Cancer Institute
  • Ministry of Education, Culture, Sports, Science and Technology, Japan

Rights:  Article is made available in accordance with the publisher's policy and may be subject to copyright law. Please refer to the publisher's site for terms of use.

Publication year: 2012
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