Genome-wide association study identifies novel breast cancer susceptibility loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-06-28

AUTHORS

Douglas F. Easton, Karen A. Pooley, Alison M. Dunning, Paul D. P. Pharoah, Deborah Thompson, Dennis G. Ballinger, Jeffery P. Struewing, Jonathan Morrison, Helen Field, Robert Luben, Nicholas Wareham, Shahana Ahmed, Catherine S. Healey, Richard Bowman, Kerstin B. Meyer, Christopher A. Haiman, Laurence K. Kolonel, Brian E. Henderson, Loic Le Marchand, Paul Brennan, Suleeporn Sangrajrang, Valerie Gaborieau, Fabrice Odefrey, Chen-Yang Shen, Pei-Ei Wu, Hui-Chun Wang, Diana Eccles, D. Gareth Evans, Julian Peto, Olivia Fletcher, Nichola Johnson, Sheila Seal, Michael R. Stratton, Nazneen Rahman, Georgia Chenevix-Trench, Stig E. Bojesen, Børge G. Nordestgaard, Christen K. Axelsson, Montserrat Garcia-Closas, Louise Brinton, Stephen Chanock, Jolanta Lissowska, Beata Peplonska, Heli Nevanlinna, Rainer Fagerholm, Hannaleena Eerola, Daehee Kang, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, David J. Hunter, Susan E. Hankinson, David G. Cox, Per Hall, Sara Wedren, Jianjun Liu, Yen-Ling Low, Natalia Bogdanova, Peter Schürmann, Thilo Dörk, Rob A. E. M. Tollenaar, Catharina E. Jacobi, Peter Devilee, Jan G. M. Klijn, Alice J. Sigurdson, Michele M. Doody, Bruce H. Alexander, Jinghui Zhang, Angela Cox, Ian W. Brock, Gordon MacPherson, Malcolm W. R. Reed, Fergus J. Couch, Ellen L. Goode, Janet E. Olson, Hanne Meijers-Heijboer, Ans van den Ouweland, André Uitterlinden, Fernando Rivadeneira, Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira, Javier Benitez, John L. Hopper, Margaret McCredie, Melissa Southey, Graham G. Giles, Chris Schroen, Christina Justenhoven, Hiltrud Brauch, Ute Hamann, Yon-Dschun Ko, Amanda B. Spurdle, Jonathan Beesley, Xiaoqing Chen, Arto Mannermaa, Veli-Matti Kosma, Vesa Kataja, Jaana Hartikainen, Nicholas E. Day, David R. Cox, Bruce A. J. Ponder

ABSTRACT

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10-7). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. More... »

PAGES

1087-1093

References to SciGraph publications

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  • Journal

    TITLE

    Nature

    ISSUE

    7148

    VOLUME

    447

    Author Affiliations

  • Department of Public Health and Primary Care and,, CR‐UK Genetic Epidemiology Unit
  • Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
  • Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, California 94043, USA.
  • Laboratory of Population Genetics, US National Cancer Institute, Bethesda, Maryland 20892, USA.
  • Department of Public Health and Primary Care, EPIC, University of Cambridge, Cambridge CB1 8RN, UK.
  • MRC Dunn Clinical Nutrition Centre, Cambridge CB2 0XY, UK.
  • Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, UK.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
  • Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
  • International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon 69008, France.
  • National Cancer Institute, Bangkok 10400, Thailand.
  • Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK.
  • Regional Genetic Service, St Mary’s Hospital, Manchester M13 0JH, UK.
  • London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK, and Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  • Breakthrough Breast Cancer Research Centre, London SW3 6JB, UK.
  • Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  • Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
  • Departments of Clinical Biochemistry and
  • Breast Surgery, Herlev and Bispebjerg University Hospitals, University of Copenhagen, DK‐2730 Herlev, Denmark.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852, USA.
  • Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
  • Cancer Center and M. Sklodowska‐Curie Institute of Oncology, Warsaw 02781, Poland.
  • Nofer Institute of Occupational Medicine, Lodz 90950, Poland.
  • Departments of Obstetrics and Gynecology, and
  • Department of Oncology, Helsinki University Central Hospital, Helsinki 00029, Finland.
  • Seoul National University College of Medicine, Seoul 151‐742, Korea.
  • National Cancer Center, Goyang 411‐769, Korea.
  • Ulsan University College of Medicine, Ulsan 680‐749, Korea.
  • Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave., Boston, Massachusetts 02115, USA.
  • Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, Massachusetts 02115, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm SE‐171 77, Sweden.
  • Population Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.
  • Department of Gynecology and Obstetrics, Hannover Medical School, D‐30625 Hannover, Germany.
  • Department of Surgery and
  • Department of Medical Decision Making and
  • Departments of Human Genetics and Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
  • Department of Medical Oncology, Family Cancer Clinic, Erasmus MC‐Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands.
  • Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.
  • Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA.
  • Institute for Cancer Studies and
  • Academic Unit of Surgical Oncology, Sheffield University Medical School, Sheffield S10 2RX, UK.
  • Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
  • Department of Clinical Genetics and
  • Internal Medicine, Erasmus University, Rotterdam NL‐3015‐GE, the Netherlands.
  • Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.
  • Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Carlton, Victoria 3053, Australia.
  • Department of Preventive and Social Medicine, University of Otago, Dunedin 9001, New Zealand.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria 3053, Australia.
  • Department of Pathology, Genetic Epidemiology Laboratory, University of Melbourne, Parkville, Victoria 3052, Australia.
  • Dr. Margarete Fischer‐Bosch‐Institute of Clinical Pharamcology, 70376 Stuttgart and University of Tuebingen, 72074 Tuebingen, Germany.
  • Deutsches Krebsforschungszentrum, Heidelberg 69120, Germany.
  • Evangelische Kliniken Bonn gGmbH Johanniter Krankenhaus, 53113 Bonn, Germany.
  • Breast Cancer Laboratory, Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
  • Medical Oncology and Clinical Haematology Unit, Western Hospital, Footscray, Victoria 3011, Australia.
  • Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.
  • Genetic Health Services Victoria, Royal Children’s Hospital, Melbourne, Victoria 3050, Australia.
  • Molecular Genetics Laboratory, Royal Brisbane and Women’s Hospital, Herston, Queensland 4029, Australia.
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature05887

    DOI

    http://dx.doi.org/10.1038/nature05887

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1027991306

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17529967


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