A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Ian P.M. Tomlinson - , Cancer Research UK (Author)
  • Emily Webb - , Institute of Cancer Research (Author)
  • Luis Carvajal-Carmona - , Cancer Research UK (Author)
  • Peter Broderick - , Institute of Cancer Research (Author)
  • Kimberley Howarth - , Cancer Research UK (Author)
  • Alan M. Pittman - , Institute of Cancer Research (Author)
  • Sarah Spain - , Cancer Research UK (Author)
  • Steven Lubbe - , Institute of Cancer Research (Author)
  • Axel Walther - , Cancer Research UK (Author)
  • Kate Sullivan - , Institute of Cancer Research (Author)
  • Emma Jaeger - , Cancer Research UK (Author)
  • Sarah Fielding - , Institute of Cancer Research (Author)
  • Andrew Rowan - , Cancer Research UK (Author)
  • Jayaram Vijayakrishnan - , Institute of Cancer Research (Author)
  • Enric Domingo - , Cancer Research UK (Author)
  • Ian Chandler - , Institute of Cancer Research (Author)
  • Zoe Kemp - , Cancer Research UK (Author)
  • Mobshra Qureshi - , Institute of Cancer Research (Author)
  • Susan M. Farrington - , University of Edinburgh (Author)
  • Albert Tenesa - , University of Edinburgh (Author)
  • James G.D. Prendergast - , University of Edinburgh (Author)
  • Rebecca A. Barnetson - , University of Edinburgh (Author)
  • Steven Penegar - , Institute of Cancer Research (Author)
  • Ella Barclay - , Cancer Research UK (Author)
  • Wendy Wood - , Institute of Cancer Research (Author)
  • Lynn Martin - , Cancer Research UK, Imperial College London, University of Birmingham (Author)
  • Maggie Gorman - , Cancer Research UK (Author)
  • Huw Thomas - , Imperial College London (Author)
  • Julian Peto - , London School of Hygiene and Tropical Medicine, Institute of Cancer Research (Author)
  • D. Timothy Bishop - , University of Leeds (Author)
  • Richard Gray - , University of Birmingham (Author)
  • Eamonn R. Maher - , University of Birmingham (Author)
  • Anneke Lucassen - , University of Southampton (Author)
  • David Kerr - , University of Oxford (Author)
  • D. Gareth R. Evans - , Imperial College London (Author)
  • Clemens Schafmayer - , Kiel University (Author)
  • Stephan Buch - , Department of internal Medicine III - Division General Medicine, Department of internal Medicine I, Kiel University, University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Henry Völzke - , University of Greifswald (Author)
  • Jochen Hampe - , Department of internal Medicine III - Division General Medicine, Department of internal Medicine I, Kiel University (Author)
  • Stefan Schreiber - , Kiel University (Author)
  • Ulrich John - , University of Greifswald (Author)
  • Thibaud Koessler - , University of Cambridge (Author)
  • Paul Pharoah - , University of Cambridge (Author)
  • Tom Van Wezel - , Leiden University (Author)
  • Hans Morreau - , Leiden University (Author)
  • Juul T. Wijnen - , Leiden University (Author)
  • John L. Hopper - , University of Melbourne (Author)
  • Melissa C. Southey - , University of Melbourne (Author)
  • Graham G. Giles - , University of Melbourne, Cancer Council Victoria (Author)
  • Gianluca Severi - , Cancer Council Victoria (Author)
  • Sergi Castellví-Bel - , University of Barcelona (Author)
  • Clara Ruiz-Ponte - , University Clinical Hospital of Santiago de Compostela (Author)
  • Angel Carracedo - , University Clinical Hospital of Santiago de Compostela (Author)
  • Antoni Castells - , University of Barcelona (Author)
  • Asta Försti - , German Cancer Research Center (DKFZ), Karolinska Institutet (Author)
  • Kari Hemminki - , German Cancer Research Center (DKFZ), Karolinska Institutet (Author)
  • Pavel Vodicka - , Czech Academy of Sciences (Author)
  • Alessio Naccarati - , Czech Academy of Sciences (Author)
  • Lara Lipton - , Western Health (Author)
  • Judy W.C. Ho - , The University of Hong Kong (Author)
  • K. K. Cheng - , The University of Hong Kong (Author)
  • Pak C. Sham - , The University of Hong Kong (Author)
  • J. Luk - , The University of Hong Kong (Author)
  • Jose A.G. Agúndez - , University of Extremadura (Author)
  • Jose M. Ladero - , Complutense University (Author)
  • Miguel De La Hoya - , Complutense University (Author)
  • Trinidad Caldés - , Complutense University (Author)
  • Iina Niittymäki - , University of Helsinki (Author)
  • Sari Tuupanen - , University of Helsinki (Author)
  • Auli Karhu - , University of Helsinki (Author)
  • Lauri Aaltonen - , University of Helsinki (Author)
  • Jean Baptiste Cazier - , Cancer Research UK (Author)
  • Harry Campbell - , University of Edinburgh (Author)
  • Malcolm G. Dunlop - , University of Edinburgh (Author)
  • Richard S. Houlston - , Institute of Cancer Research (Author)

Abstract

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10-4 in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 × 10 -13 overall; P = 6.9 × 10-12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10-18 overall; P = 9.6 × 10-17 replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.

Details

Original languageEnglish
Pages (from-to)623-630
Number of pages8
JournalNature genetics
Volume40
Issue number5
Publication statusPublished - May 2008
Peer-reviewedYes

External IDs

PubMed 18372905
ORCID /0000-0003-2928-015X/work/146166324

Keywords

Sustainable Development Goals

ASJC Scopus subject areas