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Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Author

Listed:
  • Philip J. Law

    (The Institute of Cancer Research)

  • Maria Timofeeva

    (University of Edinburgh)

  • Ceres Fernandez-Rozadilla

    (Instituto de Investigación de Santiago
    University of Birmingham)

  • Peter Broderick

    (The Institute of Cancer Research)

  • James Studd

    (The Institute of Cancer Research)

  • Juan Fernandez-Tajes

    (McCarthy Group)

  • Susan Farrington

    (University of Edinburgh)

  • Victoria Svinti

    (University of Edinburgh)

  • Claire Palles

    (University of Birmingham)

  • Giulia Orlando

    (The Institute of Cancer Research)

  • Amit Sud

    (The Institute of Cancer Research)

  • Amy Holroyd

    (The Institute of Cancer Research)

  • Steven Penegar

    (The Institute of Cancer Research)

  • Evropi Theodoratou

    (University of Edinburgh
    University of Edinburgh)

  • Peter Vaughan-Shaw

    (University of Edinburgh)

  • Harry Campbell

    (University of Edinburgh
    University of Edinburgh)

  • Lina Zgaga

    (University of Edinburgh
    University of Dublin)

  • Caroline Hayward

    (University of Edinburgh)

  • Archie Campbell

    (University of Edinburgh)

  • Sarah Harris

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Ian J. Deary

    (University of Edinburgh
    University of Edinburgh)

  • John Starr

    (University of Edinburgh
    University of Edinburgh
    University of Edinburgh)

  • Laura Gatcombe

    (University of Birmingham)

  • Maria Pinna

    (University of Birmingham)

  • Sarah Briggs

    (University of Birmingham)

  • Lynn Martin

    (University of Birmingham)

  • Emma Jaeger

    (University of Birmingham)

  • Archana Sharma-Oates

    (University of Birmingham)

  • James East

    (University of Oxford, John Radcliffe Hospital)

  • Simon Leedham

    (McCarthy Group
    University of Edinburgh)

  • Roland Arnold

    (University of Birmingham)

  • Elaine Johnstone

    (University of Oxford)

  • Haitao Wang

    (University of Oxford)

  • David Kerr

    (University of Oxford)

  • Rachel Kerr

    (University of Oxford)

  • Tim Maughan

    (University of Oxford)

  • Richard Kaplan

    (Medical Research Council Clinical Trials Unit)

  • Nada Al-Tassan

    (King Faisal Specialist Hospital and Research Center)

  • Kimmo Palin

    (University of Helsinki)

  • Ulrika A. Hänninen

    (University of Helsinki)

  • Tatiana Cajuso

    (University of Helsinki)

  • Tomas Tanskanen

    (University of Helsinki)

  • Johanna Kondelin

    (University of Helsinki)

  • Eevi Kaasinen

    (University of Helsinki)

  • Antti-Pekka Sarin

    (University of Helsinki)

  • Johan G. Eriksson

    (Folkhälsan Research Centre
    University of Helsinki and Helsinki University Hospital)

  • Harri Rissanen

    (National Institute for Health and Welfare)

  • Paul Knekt

    (National Institute for Health and Welfare)

  • Eero Pukkala

    (University of Tampere
    University of Tampere)

  • Pekka Jousilahti

    (National Institute for Health and Welfare)

  • Veikko Salomaa

    (National Institute for Health and Welfare)

  • Samuli Ripatti

    (University of Helsinki
    University of Helsinki
    Broad Institute of MIT and Harvard)

  • Aarno Palotie

    (University of Helsinki
    Massachusetts General Hospital)

  • Laura Renkonen-Sinisalo

    (Helsinki University Hospital)

  • Anna Lepistö

    (Helsinki University Hospital)

  • Jan Böhm

    (Central Finland Central Hospital)

  • Jukka-Pekka Mecklin

    (Jyväskylä Central Hospital
    University of Jyväskylä)

  • Daniel D. Buchanan

    (The University of Melbourne
    University of Melbourne, Centre for Cancer Research
    Royal Melbourne Hospital)

  • Aung-Ko Win

    (The University of Melbourne)

  • John Hopper

    (The University of Melbourne)

  • Mark E. Jenkins

    (The University of Melbourne)

  • Noralane M. Lindor

    (Mayo Clinic)

  • Polly A. Newcomb

    (Fred Hutchinson Cancer Research Center)

  • Steven Gallinger

    (Lunenfeld-Tanenbaum Research Institute)

  • David Duggan

    (Translational Genomics Research Institute (TGen), An Affiliate of City of Hope)

  • Graham Casey

    (University of Virginia)

  • Per Hoffmann

    (University of Basel
    University of Bonn)

  • Markus M. Nöthen

    (University of Bonn
    University of Bonn School of Medicine & University Hospital Bonn)

  • Karl-Heinz Jöckel

    (University of Duisburg-Essen)

  • Douglas F. Easton

    (University of Cambridge
    University of Cambridge)

  • Paul D. P. Pharoah

    (University of Cambridge
    University of Cambridge)

  • Julian Peto

    (London School of Hygiene and Tropical Medicine)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Anthony Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Rosalind A. Eeles

    (The Institute of Cancer Research
    Royal Marsden NHS Foundation Trust)

  • Zsofia Kote-Jarai

    (The Institute of Cancer Research)

  • Kenneth Muir

    (University of Manchester
    University of Warwick)

  • Nora Pashayan

    (University College London
    University of Cambridge)

  • Andrea Harkin

    (University of Glasgow)

  • Karen Allan

    (University of Glasgow)

  • John McQueen

    (University of Glasgow)

  • James Paul

    (University of Glasgow)

  • Timothy Iveson

    (University Hospital Southampton NHS Foundation Trust)

  • Mark Saunders

    (The Christie NHS Foundation Trust)

  • Katja Butterbach

    (Deutsches Krebsforschungszentrum)

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Medical Center Hamburg-Eppendorf)

  • Michael Hoffmeister

    (Deutsches Krebsforschungszentrum)

  • Hermann Brenner

    (Deutsches Krebsforschungszentrum
    German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Iva Kirac

    (Sestre milosrdnice University Hospital Centre)

  • Petar Matošević

    (University Hospital Center Zagreb)

  • Philipp Hofer

    (Medical University of Vienna)

  • Stefanie Brezina

    (Medical University of Vienna)

  • Andrea Gsur

    (Medical University of Vienna)

  • Jeremy P. Cheadle

    (Cardiff University)

  • Lauri A. Aaltonen

    (University of Helsinki)

  • Ian Tomlinson

    (University of Birmingham)

  • Richard S. Houlston

    (The Institute of Cancer Research)

  • Malcolm G. Dunlop

    (University of Edinburgh)

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.

Suggested Citation

  • 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 & Am, 2019. "Association analyses identify 31 new risk loci for colorectal cancer susceptibility," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09775-w
    DOI: 10.1038/s41467-019-09775-w
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    Citations

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    Cited by:

    1. Minta Thomas & Yu-Ru Su & Elisabeth A. Rosenthal & Lori C. Sakoda & Stephanie L. Schmit & Maria N. Timofeeva & Zhishan Chen & Ceres Fernandez-Rozadilla & Philip J. Law & Neil Murphy & Robert Carreras-, 2023. "Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Zhishan Chen & Xingyi Guo & Ran Tao & Jeroen R. Huyghe & Philip J. Law & Ceres Fernandez-Rozadilla & Jie Ping & Guochong Jia & Jirong Long & Chao Li & Quanhu Shen & Yuhan Xie & Maria N. Timofeeva & Mi, 2024. "Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Stephanie A. Schubert & Dina Ruano & Sebastien M. Joruiz & Jordy Stroosma & Nikolina Glavak & Anna Montali & Lia M. Pinto & Mar Rodríguez-Girondo & Daniela Q. C. M. Barge-Schaapveld & Maartje Nielsen , 2024. "Germline variant affecting p53β isoforms predisposes to familial cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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