Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Research output: Contribution to journalArticle

Authors

  • PRACTICAL consortium

Colleges, School and Institutes

External organisations

  • Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
  • Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.
  • Wellcome Centre for Human Genetics, McCarthy Group, Roosevelt Drive, Oxford, OX3 7BN, UK.
  • Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.
  • Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, EH8 9AG, UK.
  • Department of Public Health and Primary Care, Institute of Population Health, Trinity College Dublin, University of Dublin, Dublin, D02 PN40, Ireland.
  • Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. a.kilgour@ed.ac.uk.
  • Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Translational Gastroenterology Unit, Nuffield Department. of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  • Cancer Bioinfomatics Laboratory, Institute of Cancer and Genomic Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK.
  • Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7LE, UK.
  • Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
  • Medical Research Council Clinical Trials Unit, Aviation House, 125 Kingsway, London, WC2B 6NH, UK.
  • Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.
  • Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, 00014, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, 00014, Finland.
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland.
  • National Institute for Health and Welfare, Helsinki, 00271, Finland; Folkhälsan Research Centre, Helsinki, 00250, Finland; Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, 00014, Finland.
  • National Institute for Health and Welfare, Helsinki, 00271, Finland.
  • Faculty of Social Sciences, University of Tampere, Tampere, 33014, Finland.

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.

Details

Original languageEnglish
Article number2154
Number of pages15
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 14 May 2019