Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci

Research output: Contribution to journalArticle

Authors

  • Tomas Tanskanen
  • Linda van den Berg
  • Niko Välimäki
  • Mervi Aavikko
  • Eivind Ness-Jensen
  • And 55 others
  • Kristian Hveem
  • Yvonne Wettergren
  • Elinor Bexe Lindskog
  • Neeme Tõnisson
  • Andres Metspalu
  • Kaisa Silander
  • Giulia Orlando
  • Philip J Law
  • Sari Tuupanen
  • Alexandra E Gylfe
  • Ulrika A Hänninen
  • Tatiana Cajuso
  • Johanna Kondelin
  • Antti-Pekka Sarin
  • Eero Pukkala
  • Pekka Jousilahti
  • Veikko Salomaa
  • Samuli Ripatti
  • Aarno Palotie
  • Heikki Järvinen
  • Laura Renkonen-Sinisalo
  • Anna Lepistö
  • Jan Böhm
  • Jukka-Pekka Mecklin
  • Nada A Al-Tassan
  • Claire Palles
  • Lynn Martin
  • Ella Barclay
  • Albert Tenesa
  • Susan M Farrington
  • Maria N Timofeeva
  • Brian F Meyer
  • Salma M Wakil
  • Harry Campbell
  • Christopher G Smith
  • Shelley Idziaszczyk
  • Tim S Maughan
  • Richard Kaplan
  • Rachel Kerr
  • David Kerr
  • Daniel D Buchanan
  • Aung K Win
  • John Hopper
  • Mark A Jenkins
  • Polly A Newcomb
  • Steve Gallinger
  • David Conti
  • Fredrick R Schumacher
  • Graham Casey
  • Jeremy P Cheadle
  • Malcolm G Dunlop
  • Ian P Tomlinson
  • Richard S Houlston
  • Kimmo Palin
  • Lauri A Aaltonen

Colleges, School and Institutes

External organisations

  • Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
  • Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
  • K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
  • Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • National Institute for Health and Welfare, Helsinki, Finland.
  • Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Faculty of Social Sciences, University of Tampere, Tampere, Finland.
  • National Institute for Health & Welfare, Helsinki, Finland.
  • Department of Neurology, Massachusetts General Hospital, Boston, MA.
  • Department of Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
  • Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
  • Department of Surgery, Jyväskylä Central Hospital, University of Eastern Finland, Jyväskylä, Finland.
  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
  • Wellcome Trust Centre for Human Genetics and NIHR Comprehensive Biomedical Research Centre, Oxford, United Kingdom.
  • Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
  • University of Edinburgh, The
  • Colon Cancer Genetics Group, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
  • From the Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom (J.P.S., R.S., C.H., F.D.R.H., D.N., A.W., R.J.M.); Institute of Applied Health Research, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom (P.G., U.M.); Family Practice Unit, Memorial University of Newfoundland, St John's, Newfoundland, NL, Canada (M.G.); Health Services Research Unit, Edinburgh Napier University, Edinburgh, United Kingdom (J.H.); Cambridge Institute of Public Health, University of Cambridge, Cambridge, United Kingdom (J.M.); Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom (B.M.); Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada (M.M.); and Institute of Cardiovascular Science, University College London, London, United Kingdom (B.W.). james.sheppard@phc.ox.ac.uk.
  • Cardiff University
  • 5. CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
  • MRC Clinical Trials Unit, , Aviation House, London, United Kingdom.
  • Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
  • Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Vic, Australia.
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA.

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.

Details

Original languageEnglish
Pages (from-to)540-546
Number of pages7
JournalInternational Journal of Cancer
Volume142
Issue number3
Early online date12 Oct 2017
Publication statusPublished - 9 Dec 2018

Keywords

  • Case-Control Studies, Cohort Studies, Colorectal Neoplasms, Estonia, Finland, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Registries, Journal Article, Meta-Analysis