Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Philip Law(Institute of Cancer Research), Maria Timofeeva(Western General Hospital), Ceres Fernández–Rozadilla(Fundación Pública Galega de Medicina Xenómica), Peter Broderick(Institute of Cancer Research), James B. Studd(Institute of Cancer Research), Juan Fernández‐Tajes(Centre for Human Genetics), Susan M. Farrington(Western General Hospital), Victoria Svinti(Western General Hospital), Claire Palles(University of Birmingham), Giulia Orlando(Institute of Cancer Research), Amit Sud(Institute of Cancer Research), Amy Holroyd(Institute of Cancer Research), Steven Penegar(Institute of Cancer Research), Evropi Τheodoratou(Western General Hospital), P G Vaughan-Shaw(Western General Hospital), Harry Campbell(Western General Hospital), Lina Zgaga(Trinity College Dublin), Caroline Hayward(Western General Hospital), Archie Campbell(Institute of Genetics and Cancer), Sarah E. Harris(Institute of Genetics and Cancer), Ian J. Deary(Institute of Genetics and Cancer), John M. Starr(Alzheimer Scotland), 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 E. East(John Radcliffe Hospital), Simon J. Leedham(Centre for Human Genetics), Roland Arnold(University of Birmingham), Elaine Johnstone(University of Oxford), Haitao Wang(University of Oxford), David Kerr(John Radcliffe Hospital), Rachel Kerr(University of Oxford), Tim Maughan(University of Oxford), Richard Kaplan(Medical Research Council), Nada Al Tassan(King Faisal Specialist Hospital & Research Centre), 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(University of Helsinki), Harri Rissanen(Finnish Institute for Health and Welfare), Paul Knekt(Finnish Institute for Health and Welfare), Eero Pukkala(Finnish Cancer Registry), Pekka Jousilahti(Finnish Institute for Health and Welfare), Veikko Salomaa(Finnish Institute for Health and Welfare), Samuli Ripatti(Broad Institute), Aarno Palotie(University of Helsinki), Laura Renkonen‐Sinisalo(Helsinki University Hospital), Anna Lepistö(Helsinki University Hospital), J. Böhm(Central Finland Health Care District), Jukka‐Pekka Mecklin(Central Finland Health Care District), Daniel D. Buchanan(The Royal Melbourne Hospital), Aung Ko Win(The University of Melbourne), John L. Hopper(The University of Melbourne), Mark A. Jenkins(The University of Melbourne), Noralane M. Lindor(Mayo Clinic in Arizona), Polly A. Newcomb(Fred Hutch Cancer Center), Steven Gallinger(Mount Sinai Hospital), David Duggan(Translational Genomics Research Institute), Graham Casey(University of Virginia), Per Hoffmann(University of Bonn), Markus M. Nöthen(University of Bonn), Karl‐Heinz Jöckel(University of Duisburg-Essen), Douglas F. Easton(University of Cambridge), Paul D.P. Pharoah(University of Cambridge), Julian Peto(London School of Hygiene & Tropical Medicine), Federico Canzian(German Cancer Research Center), Anthony J. Swerdlow(Institute of Cancer Research), Rosalind A. Eeles(Royal Marsden NHS Foundation Trust), Zsofia Kote‐Jarai(Institute of Cancer Research), Kenneth Muir(Manchester Academic Health Science Centre), Nora Pashayan(University of Cambridge), Brian E. Henderson(University of Southern California), Christopher A. Haiman(University of Southern California), Fredrick R. Schumacher(University Hospitals Seidman Cancer Center), Ali Amin Al Olama(University of Cambridge), Sara Benlloch(University of Cambridge), Sonja I. Berndt(National Cancer Institute), David V. Conti(University of Southern California), Fredrik Wiklund(Karolinska Institutet), Stephen J. Chanock(University of Southern California), Susan M. Gapstur(American Cancer Society), Victoria L. Stevens(American Cancer Society), Catherine M. Tangen(Fred Hutch Cancer Center), Jyotsna Batra(Translational Research Institute), Judith A. Clements(Translational Research Institute), Henrik Grönberg(Karolinska Institutet), Johanna Schleutker(University of Turku), Demetrius Albanes(National Cancer Institute), Alicja Wolk(Uppsala University), Catharine West(Manchester Academic Health Science Centre), Lorelei A. Mucci(Harvard University), Géraldine Cancel‐Tassin(Sorbonne Université), Stella Koutros(National Cancer Institute), Karina D. Sørensen(Aarhus University), Eli Marie Grindedal(Oslo University Hospital), David E. Neal(University of Cambridge), Freddie C. Hamdy(John Radcliffe Hospital), Jenny Donovan(University of Bristol), Ruth C. Travis(University of Oxford), Robert J. Hamilton(Princess Margaret Cancer Centre), Sue A. Ingles(University of Southern California), Barry S. Rosenstein(Icahn School of Medicine at Mount Sinai), Yong‐Jie Lu(Queen Mary University of London), Graham G. Giles(The University of Melbourne), Adam S. Kibel(Brigham and Women's Hospital), Ana Vega(Fundación Pública Galega de Medicina Xenómica), Manolis Kogevinas(Universitat Pompeu Fabra), Kathryn L. Penney(Brigham and Women's Hospital), Jong Y. Park(Moffitt Cancer Center), Janet L. Stanford(Fred Hutch Cancer Center), Cezary Cybulski(International Hereditary Cancer Center), Børge G. Nordestgaard(University of Copenhagen), Christiane Maier(University Hospital Ulm), Jeri Kim(The University of Texas MD Anderson Cancer Center), Esther M. John(Cancer Prevention Institute of California), Manuel R. Teixeira(Universidade do Porto), Susan L. Neuhausen(City of Hope), Kim De Ruyck(Ghent University), Azad Hassan Abdul Razack(University of Malaya), Lisa F. Newcomb(Fred Hutch Cancer Center), Marija Gamulin(University Hospital Centre Zagreb), Radka Kaneva(Medical University of Sofia), Nawaid Usmani(University of Alberta), Frank Claessens(KU Leuven), Paul A. Townsend(Manchester Academic Health Science Centre), Manuela Gago-Domínguez(University of California San Diego), Monique J. Roobol(Erasmus MC), F. Ménégaux(Inserm), Kay‐Tee Khaw(University of Cambridge), Lisa Cannon‐Albright(University of Utah), Hardev Pandha(University of Surrey), Stephen N. Thibodeau(Mayo Clinic in Arizona), Andrea Harkin(Cancer Research UK), Karen Allan(Cancer Research UK), John McQueen(Cancer Research UK), James Paul(Cancer Research UK), Timothy Iveson(University Hospital Southampton NHS Foundation Trust), Mark Saunders(The Christie NHS Foundation Trust), Katja Butterbach(German Cancer Research Center), Jenny Chang‐Claude(Universität Hamburg), Michael Hoffmeister(German Cancer Research Center), Hermann Brenner(German Cancer Research Center), Iva Kirac(University Hospital Centre Zagreb), Petar Matošević(University Hospital Centre 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(Institute of Cancer Research), Malcolm G. Dunlop(Western General Hospital)
Cited by 272Open Access
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.
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