Genome-wide association study identifies novel breast cancer susceptibility loci (original) (raw)

Change history

In the AOP version of this Article, Kristy Driver was omitted from The SEARCH collaborators. This and the Supplementary Information acknowledgements have now been corrected for both print and online publication on 28 June 2007.

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Acknowledgements

The authors thank the women who took part in this research, and all the funders and support staff who made this study possible. The principal funding for this study was provided by Cancer Research UK. Detailed acknowledgements are provided in Supplementary Information.

Author Contributions D.F.E., A.M.D., P.D.P.P., D.R.C. and B.A.J.P. designed the study and obtained financial support. D.G.B. and D.R.C. directed the genotyping of stages 1 and 2. D.F.E. and D.T. conducted the statistical analysis. K.A.P. and A.M.D. coordinated the genotyping for stage 3 and the fine-scale mapping of the FGFR2 and TNRC9 loci. J.P.S. and J.Z. performed resequencing and analysis of the FGFR2 locus. K.A.P., S.A., C.S.H., R.B., C.A.H., L.K.K., B.E.H., L.L.M., P.B., S.S., V.G., F.O., C-Y. S., P-E.W. and H-C.W. conducted genotyping for the fine-scale mapping. R.L., J.M., H.F. and K.B.M. provided bioinformatics support. D.E., D.G.E., J.P., O.F., N.J., S.S., M.R.S. and N.R. coordinated the studies used in stage 1. N.W. and N.E.D. coordinated the EPIC study used in stages 1 and 2. The remaining authors coordinated the studies in stage 3 and undertook genotyping in those studies. D.F.E. drafted the manuscript, with substantial contributions from K.A.P., A.M.D., P.D.P.P. and B.A.J.P. All authors contributed to the final paper.

Author information

Author notes

  1. Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
  2. Insitute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio, Kuopio FIN‐70210, Finland.
  3. Departments of Oncology and Pathology, University Hospital of Kuopio, Kuopio FIN‐70211, Finland.
  4. Department of Oncology, Vaasa Central Hospital, Vaasa 65130, Finland.
  5. Lists of consortia participants and affiliations appear after author affiliations.

Authors and Affiliations

  1. Department of Public Health and Primary Care and,, CR‐UK Genetic Epidemiology Unit,
    Douglas F. Easton & Deborah Thompson
  2. Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.,
    Karen A. Pooley, Alison M. Dunning, Paul D. P. Pharoah, Jonathan Morrison, Helen Field, Shahana Ahmed & Catherine S. Healey
  3. Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, California 94043, USA.,
    Dennis G. Ballinger
  4. Laboratory of Population Genetics, US National Cancer Institute, Bethesda, Maryland 20892, USA.,
    Jeffery P. Struewing & Jinghui Zhang
  5. Department of Public Health and Primary Care, EPIC, University of Cambridge, Cambridge CB1 8RN, UK.,
    Robert Luben & Nicholas Wareham
  6. MRC Dunn Clinical Nutrition Centre, Cambridge CB2 0XY, UK.,
    Richard Bowman
  7. Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, UK.,
    Kerstin B. Meyer
  8. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.,
    Christopher A. Haiman & Brian E. Henderson
  9. Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.,
    Laurence K. Kolonel & Loic Le Marchand
  10. International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon 69008, France.,
    Paul Brennan, Valerie Gaborieau & Fabrice Odefrey
  11. National Cancer Institute, Bangkok 10400, Thailand.,
    Suleeporn Sangrajrang
  12. Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.,
    Chen-Yang Shen, Pei-Ei Wu & Hui-Chun Wang
  13. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK.,
    Diana Eccles
  14. Regional Genetic Service, St Mary’s Hospital, Manchester M13 0JH, UK.,
    D. Gareth Evans
  15. London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK, and Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.,
    Julian Peto
  16. Breakthrough Breast Cancer Research Centre, London SW3 6JB, UK.,
    Olivia Fletcher & Nichola Johnson
  17. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.,
    Sheila Seal, Michael R. Stratton & Nazneen Rahman
  18. Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.,
    Michael R. Stratton
  19. Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.,
    Georgia Chenevix-Trench, Amanda B. Spurdle, Jonathan Beesley & Xiaoqing Chen
  20. Departments of Clinical Biochemistry and,
    Stig E. Bojesen & Børge G. Nordestgaard
  21. Breast Surgery, Herlev and Bispebjerg University Hospitals, University of Copenhagen, DK‐2730 Herlev, Denmark.,
    Christen K. Axelsson
  22. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852, USA.,
    Montserrat Garcia-Closas & Louise Brinton
  23. Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland 20877, USA.,
    Stephen Chanock
  24. Cancer Center and M. Sklodowska‐Curie Institute of Oncology, Warsaw 02781, Poland.,
    Jolanta Lissowska
  25. Nofer Institute of Occupational Medicine, Lodz 90950, Poland.,
    Beata Peplonska
  26. Departments of Obstetrics and Gynecology, and,
    Heli Nevanlinna, Rainer Fagerholm & Hannaleena Eerola
  27. Department of Oncology, Helsinki University Central Hospital, Helsinki 00029, Finland.,
    Hannaleena Eerola
  28. Seoul National University College of Medicine, Seoul 151‐742, Korea.,
    Daehee Kang, Keun-Young Yoo & Dong-Young Noh
  29. National Cancer Center, Goyang 411‐769, Korea.,
    Keun-Young Yoo
  30. Ulsan University College of Medicine, Ulsan 680‐749, Korea.,
    Sei-Hyun Ahn
  31. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, Massachusetts 02115, USA.,
    David J. Hunter & David G. Cox
  32. Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave., Boston, Massachusetts 02115, USA.,
    David J. Hunter & Susan E. Hankinson
  33. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm SE‐171 77, Sweden.,
    Per Hall & Sara Wedren
  34. Population Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.,
    Jianjun Liu & Yen-Ling Low
  35. Department of Radiation Oncology and,
    Natalia Bogdanova
  36. Department of Gynecology and Obstetrics, Hannover Medical School, D‐30625 Hannover, Germany.,
    Natalia Bogdanova, Peter Schürmann & Thilo Dörk
  37. Department of Surgery and,
    Rob A. E. M. Tollenaar
  38. Department of Medical Decision Making and,
    Catharina E. Jacobi
  39. Departments of Human Genetics and Pathology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.,
    Peter Devilee
  40. Department of Medical Oncology, Family Cancer Clinic, Erasmus MC‐Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands.,
    Jan G. M. Klijn
  41. Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.,
    Alice J. Sigurdson & Michele M. Doody
  42. Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA.,
    Bruce H. Alexander
  43. Institute for Cancer Studies and,
    Angela Cox, Ian W. Brock & Gordon MacPherson
  44. Academic Unit of Surgical Oncology, Sheffield University Medical School, Sheffield S10 2RX, UK.,
    Malcolm W. R. Reed
  45. Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.,
    Fergus J. Couch, Ellen L. Goode & Janet E. Olson
  46. VU University Medical Center, 1007 MB Amsterdam, the Netherlands.,
    Hanne Meijers-Heijboer
  47. Department of Clinical Genetics and,
    Hanne Meijers-Heijboer & Ans van den Ouweland
  48. Internal Medicine, Erasmus University, Rotterdam NL‐3015‐GE, the Netherlands.,
    André Uitterlinden & Fernando Rivadeneira
  49. Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.,
    Roger L. Milne, Gloria Ribas, Anna Gonzalez-Neira & Javier Benitez
  50. Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Carlton, Victoria 3053, Australia.,
    John L. Hopper & Melissa Southey
  51. Department of Preventive and Social Medicine, University of Otago, Dunedin 9001, New Zealand.,
    Margaret McCredie
  52. Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria 3053, Australia.,
    Graham G. Giles
  53. Department of Pathology, Genetic Epidemiology Laboratory, University of Melbourne, Parkville, Victoria 3052, Australia.,
    Chris Schroen
  54. Dr. Margarete Fischer‐Bosch‐Institute of Clinical Pharamcology, 70376 Stuttgart and University of Tuebingen, 72074 Tuebingen, Germany.,
    Christina Justenhoven & Hiltrud Brauch
  55. Deutsches Krebsforschungszentrum, Heidelberg 69120, Germany.,
    Ute Hamann
  56. Evangelische Kliniken Bonn gGmbH Johanniter Krankenhaus, 53113 Bonn, Germany.,
    Yon-Dschun Ko
  57. Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.,
    Craig Luccarini, Don Conroy, Mitul Shah, Hannah Munday, Clare Jordan, Barbara Perkins, Judy West, Karen Redman & Kristy Driver
  58. Oncology Research Centre, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.,
    Morteza Aghmesheh & Bruce A. J. Ponder
  59. Genetic Health Services Victoria, Royal Children’s Hospital, Melbourne, Victoria 3050, Australia.,
    David Amor & David R. Cox
  60. Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.,
    Lesley Andrews, Barbara Bennett, Bettina Meiser, Kathy Tucker & Janet Tyler
  61. Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.,
    Yoland Antill, Sarah-Jane Dawson, Kelly Phillips, Clare Scott & Nicholas E. Day
  62. Anatomical Pathology, Royal Women’s Hospital, Carlton, Victoria 3053, Australia.,
    Jane Armes
  63. Molecular Genetics Laboratory, Royal Brisbane and Women’s Hospital, Herston, Queensland 4029, Australia.,
    Shane Armitage, Leanne Arnold, Alison Jones & Bruce A. J. Ponder
  64. Departments of Translational and Medical Oncology, Westmead Hospital, Westmead, New South Wales 2145, Australia.,
    Rosemary Balleine
  65. Cancer Biology Laboratory, TVW Institute for Child Health Research, Subiaco, Western Australia 6008, Australia.,
    Glenn Begley
  66. Pathology Centre, Queen Elizabeth Medical Centre, Nedlands, Western Australia 6009, Australia.,
    John Beilby
  67. Silverton Place, 101 Wickham Terrace, Brisbane, Queensland 4000, Australia.,
    Ian Bennett
  68. Department of Public Health and Community Medicine, University of Sydney, Sydney, New South Wales 2006, Australia.,
    Geoffrey Berry
  69. John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, Australian Capital Territory 2601, Australia.,
    Anneke Blackburn
  70. NSW Breast Cancer Institute, PO Box 143, Westmead, New South Wales 2145, Australia.,
    Meagan Brennan
  71. Department of Biochemistry, University of Queensland, St. Lucia, Queensland 4072, USA.,
    Melissa Brown
  72. Molecular and Cytogenetics Unit, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.,
    Michael Buckley
  73. Royal Hobart Hospital, GPO Box 1061L, Hobart, Tasmania 7001, Australia.,
    Jo Burke & Evelyn Humphrey
  74. Medical Psychology Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales 2204, Australia.,
    Phyllis Butow
  75. Australian Genome Research Facility, Walter & Eliza Hall Medical Research Institute, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.,
    Keith Byron
  76. Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide/Hanson Institute, PO Box 14, Rundle Mall, South Australia 5000, Australia.,
    David Callen
  77. Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria 3002, Australia.,
    Ian Campbell, Joe Sambrook & Heather Thorne
  78. Queensland Institute of Medical Research, Herston, Queensland 4006, Australia.,
    Georgia Chenevix-Trench, Nick Hayward, Amanda Spurdle, Adele Green, Georgia Chenevix-Trench & Penny Webb
  79. Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital ,Westmead, New South Wales 2145, Australia.,
    Christine Clarke & Graham Mann
  80. Department of Clinical Genetics, Liverpool Health Service, PO Box 103, Liverpool, New South Wales 2170, Australia.,
    Alison Colley
  81. Mutation Research Centre, St Vincent’s Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia.,
    Dick Cotton
  82. Centre for Genetic Epidemiology, The University of Melbourne, Level 2 723 Swanston Street, Carlton, Victoria 3053, Australia.,
    Jisheng Cui, Roger Milne & Melissa Southey
  83. Molecular and Clinical Genetics, Level 1 Building 65, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.,
    Bronwyn Culling
  84. Department of Pathology, University of Queensland Medical School, Herston, New South Wales 4006, Australia.,
    Margaret Cummings
  85. Central Regional Genetic Services, Wellington Hospital, Private bag 7902, Wellington South 6039, New Zealand.,
    Joanne Dixon
  86. Molecular Department of Pathology, Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria 3002, Australia.,
    Alexander Dobrovic & Paul Waring
  87. Hunter Genetics, Hunter Area Health Service, Waratah, New South Wales 2310, Australia.,
    Tracy Dudding & Rodney Scott
  88. Clinical Chemistry, Princess Margret Hospital for Children, Box D184, Perth, Western Australia 6001, Australia.,
    Ted Edkins
  89. Department of Multicultural Health, University of Sydney, New South Wales 2052, Australia.,
    Maurice Eisenbruch
  90. Tissue Pathology, Institute of Medical & Veterinary Science, Adelaide, South Australia 5000, Australia.,
    Gelareh Farshid
  91. Family Cancer Clinic, Monash Medical Centre, Clayton, Victoria 3168, Australia.,
    Susan Fawcett
  92. Faculty of Medicine, Royal North Shore Hospital, Vindin House, St Leonards, New South Wales 2065, Australia.,
    Michael Field
  93. Department of Haematology, Flinders Medical Centre, Bedford Park, South Australia 5042, Australia.,
    Frank Firgaira, Scott Grist & Ram Seshadri
  94. Eskitis Institute of Cell & Molecular Therapies, School of Biomolecular and Biomedical Sciences, Griffith University, Nathan, Queensland 4111, Australia.,
    Jean Fleming
  95. Surgical Oncology, University of Newcastle, Newcastle Mater Hospital, Waratah, New South Wales 2298, Australia.,
    John Forbes
  96. Department of Medical Oncology, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.,
    Michael Friedlander
  97. Victorian Clinical Genetics Service, Royal Melbourne Hospital, Parkville, Victoria 3052, Australia.,
    Clara Gaff & Mac Gardner
  98. Queensland Clinical Genetic Service, Royal Children’s Hospital, Bramston Terrace, Herston, Queensland 4020, Australia.,
    Mike Gattas
  99. Clinical Biochemistry Unit, Canterbury Health Labs, PO Box 151, Christchurch 8140, New Zealand.,
    Peter George
  100. Cancer Epidemiology Centre, The Cancer Council Victoria, 1 Rathdowne Street, Carlton, Victoria 3053, Australia.,
    Graham Giles
  101. Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.,
    Grantley Gill
  102. Genetic Services of WA, King Edward Memorial Hospital, 374 Bagot Road, Subiaco, Western Australia 6008, Australia.,
    Jack Goldblatt, Sharron Townshend & Ian Walpole
  103. Wollongong Hereditary Cancer Clinic, Wollongong Public Hospital, Private Mail Bag 8808, South Coast Mail Centre, New South Wales 2521, Australia.,
    Sian Greening
  104. Department of Medical Genetics, Women’s and Children’s Hospital, North Adelaide, South Australia 5006, Australia.,
    Eric Haan & Graeme Suthers
  105. Familial Cancer Clinic, Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria 3002, Australia.,
    Marion Harris, Michael McKay, Gillian Mitchell & Mary Ann Young
  106. Breast and Ovarian Cancer Genetics, Monash Medical Centre, 871 Centre Road, Bentleigh East, Victoria 3165, Australia.,
    Stewart Hart
  107. Centre for Molecular Environmental, Genetic & Analytic Epidemiology, University of Melbourne, Melbourne, Victoria 3010, Australia.,
    John Hopper, Richard Osborne & Dorota Gertig
  108. School of Population Health, The University of Melbourne, 723 Swanston Street, Carlton, Victoria 3053, Australia.,
    Mark Jenkins
  109. Medical Oncology, Westmead Hospital, Westmead, New South Wales 2145, Australia.,
    Rick Kefford
  110. Department of Medicine, Familial Cancer Service, Westmead Hospital, Westmead, New South Wales 2145, Australia.,
    Judy Kirk & Jennifer Leary
  111. Breast Endocrine and Surgical Unit, Royal Adelaide Hospital, North Terrace, South Australia 5000, Australia.,
    James Kollias
  112. Molecular Pathology Department, Southern Cross Pathology, Monash Medical Centre, Clayton, Victoria 3168, Australia.,
    Sergey Kovalenko
  113. Molecular and Cellular Pathology, The University of Queensland, Herston, Queensland 4006, Australia.,
    Sunil Lakhani
  114. Department of Psychological Medicine, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.,
    Jacqueline Lim, Christopher Tennant, Arto Mannermaa, Veli-Matti Kosma, Vesa Kataja & Jaana Hartikainen
  115. Breast Cancer Laboratory, Walter and Eliza Hall Institute, PO Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.,
    Geoff Lindeman, Arto Mannermaa, Veli-Matti Kosma & Jaana Hartikainen
  116. Medical Oncology and Clinical Haematology Unit, Western Hospital, Footscray, Victoria 3011, Australia.,
    Lara Lipton & Vesa Kataja
  117. WA Centre for Cancer, Edith Cowan University, Churchlands, Western Australia 6018, Australia.,
    Liz Lobb
  118. Department of Psychological Medicine, University of Sydney, New South Wales 2006, Australia.,
    Mariette Maclurcan & Melanie Price
  119. Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.,
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  120. Cancer Epidemiology Research Unit, NSW Cancer Council, 153 Dowling Street, Woolloomooloo, New South Wales 2011, Australia.,
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  121. Department of Oncology, St Vincent’s Hospital, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.,
    Sue Anne McLachlan
  122. School of Public Health, Queensland University of Technology, Victoria Park, Kelvin Grove, Queensland 4059, Australia.,
    Beth Newman
  123. St Vincent’s Breast Clinic, PO Box 4751, Toowoomba, Queensland 4350, Australia.,
    Imelda O’Loughlin, Graham Warren & Elizabeth Watson
  124. Radiation Oncology, Peter MacCallum Cancer Centre, St Andrew’s Place, East Melbourne, Victoria 3002, Australia.,
    Lester Peters
  125. Genetic Services, Auckland Hospital, Private Bag 92024, Auckland 1142, New Zealand.,
    Jeanne Reeve & Ingrid Winship
  126. Cancer Genetics Laboratory, University of Otago, PO Box 56, Dunedin 9054, New Zealand.,
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  127. Department of Cytogenetics and Molecular Genetics, Women and Children’s Hospital, Adelaide, South Australia 5006, Australia.,
    Robert Richards
  128. Hancock Family Breast Cancer Foundation, PO Locked Bag 2, West Perth, Western Australia 6005, Australia.,
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  130. Molecular Pathology Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia.,
    Barney Rudzki
  131. Section of Cytology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales 2145, Australia.,
    Elizabeth Salisbury
  132. School of Surgery and Pathology, QE11 Medical Centre, M block 2nd Floor, Nedlands, Western Australia 6907, Australia.,
    Christobel Saunders
  133. South View Clinic, Suite 13, Level 3 South Street, Kogarah, New South Wales 2217, Australia.,
    Elizabeth Scott
  134. Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.,
    Andrew Shelling
  135. Department of Radiology, Royal Perth Hospital, Box X2213, Perth 6011, Western Australia, Australia.,
    Donna Taylor
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  1. Douglas F. Easton
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Correspondence toDouglas F. Easton.

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

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Easton, D., Pooley, K., Dunning, A. et al. Genome-wide association study identifies novel breast cancer susceptibility loci.Nature 447, 1087–1093 (2007). https://doi.org/10.1038/nature05887

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