Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-10-24

AUTHORS

Richard S Houlston, Jeremy Cheadle, Sara E Dobbins, Albert Tenesa, Angela M Jones, Kimberley Howarth, Sarah L Spain, Peter Broderick, Enric Domingo, Susan Farrington, James GD Prendergast, Alan M Pittman, Evi Theodoratou, Christopher G Smith, Bianca Olver, Axel Walther, Rebecca A Barnetson, Michael Churchman, Emma EM Jaeger, Steven Penegar, Ella Barclay, Lynn Martin, Maggie Gorman, Rachel Mager, Elaine Johnstone, Rachel Midgley, Iina Niittymäki, Sari Tuupanen, James Colley, Shelley Idziaszczyk, , Huw JM Thomas, Anneke M Lucassen, D Gareth R Evans, Eamonn R Maher, , , , Timothy Maughan, Antigone Dimas, Emmanouil Dermitzakis, Jean-Baptiste Cazier, Lauri A Aaltonen, Paul Pharoah, David J Kerr, Luis G Carvajal-Carmona, Harry Campbell, Malcolm G Dunlop, Ian PM Tomlinson

ABSTRACT

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10⁻¹⁰ and rs6687758, OR = 1.09, P = 2.27 × 10⁻⁹, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10⁻⁸), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10⁻¹⁰ and rs7136702, OR = 1.06, P = 4.02 × 10⁻⁸) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10⁻¹⁰). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered. More... »

PAGES

973-977

Journal

TITLE

Nature Genetics

ISSUE

11

VOLUME

42

Author Affiliations

  • Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, United Kingdom
  • Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom
  • Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Edinburgh EH4 2XU, United Kingdom
  • Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN. United Kingdom
  • Department of Clinical Pharmacology, Oxford University, Radcliffe Infirmary, Old Road Campus Research Building, Headington, Oxford, OX3 7DQ, United Kingdom
  • Department of Medical Genetics, Genome-Scale Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
  • Colorectal Cancer Unit, Cancer Research UK, St Mark's Hospital, Harrow HA1 3UJ, UK
  • Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK
  • Medical Genetics, St Mary's Hospital, Manchester M13 0JH, UK
  • Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham, Institute of Biomedical Research, and West Midlands Regional Genetics Service, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TT, UK
  • Department of Oncology and Palliative Care, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
  • Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva CH-1211, Switzerland
  • Cancer Research UK Laboratories, Strangeways Research Laboratory Department of Oncology, University of Cambridge, Cambridge CB1 8RN, United Kingdom
  • SIDRA Medical & Research Center, Qatar Foundation, PO Box 26999, Doha, Qatar
  • Public Health Sciences, University of Edinburgh, EH8 9AG, United Kingdom
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.670

    DOI

    http://dx.doi.org/10.1038/ng.670

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1019770596

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20972440


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