Genome-wide association study identifies novel breast cancer susceptibility loci

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 and Bruce A. J. Ponder
Additional contact information
Douglas F. Easton: CR‐UK Genetic Epidemiology Unit
Karen A. Pooley: University of Cambridge, Cambridge CB1 8RN, UK.
Alison M. Dunning: University of Cambridge, Cambridge CB1 8RN, UK.
Paul D. P. Pharoah: University of Cambridge, Cambridge CB1 8RN, UK.
Deborah Thompson: CR‐UK Genetic Epidemiology Unit
Dennis G. Ballinger: Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, California 94043, USA.
Jeffery P. Struewing: Laboratory of Population Genetics, US National Cancer Institute, Bethesda, Maryland 20892, USA.
Jonathan Morrison: University of Cambridge, Cambridge CB1 8RN, UK.
Helen Field: University of Cambridge, Cambridge CB1 8RN, UK.
Robert Luben: EPIC, University of Cambridge, Cambridge CB1 8RN, UK.
Nicholas Wareham: EPIC, University of Cambridge, Cambridge CB1 8RN, UK.
Shahana Ahmed: University of Cambridge, Cambridge CB1 8RN, UK.
Catherine S. Healey: University of Cambridge, Cambridge CB1 8RN, UK.
Richard Bowman: MRC Dunn Clinical Nutrition Centre, Cambridge CB2 0XY, UK.
Kerstin B. Meyer: Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, UK.
Christopher A. Haiman: Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Laurence K. Kolonel: Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
Brian E. Henderson: Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Loic Le Marchand: Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813, USA.
Paul Brennan: International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon 69008, France.
Suleeporn Sangrajrang: National Cancer Institute, Bangkok 10400, Thailand.
Valerie Gaborieau: International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon 69008, France.
Fabrice Odefrey: International Agency for Research on Cancer, 150 Cours Albert Thomas, Lyon 69008, France.
Chen-Yang Shen: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Pei-Ei Wu: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Hui-Chun Wang: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Diana Eccles: Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton SO16 5YA, UK.
D. Gareth Evans: Regional Genetic Service, St Mary’s Hospital, Manchester M13 0JH, UK.
Julian Peto: London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK, and Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Olivia Fletcher: Breakthrough Breast Cancer Research Centre, London SW3 6JB, UK.
Nichola Johnson: Breakthrough Breast Cancer Research Centre, London SW3 6JB, UK.
Sheila Seal: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Michael R. Stratton: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Nazneen Rahman: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Georgia Chenevix-Trench: Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
Stig E. Bojesen: Departments of Clinical Biochemistry and
Børge G. Nordestgaard: Departments of Clinical Biochemistry and
Christen K. Axelsson: Breast Surgery, Herlev and Bispebjerg University Hospitals, University of Copenhagen, DK‐2730 Herlev, Denmark.
Montserrat Garcia-Closas: National Cancer Institute, Rockville, Maryland 20852, USA.
Louise Brinton: National Cancer Institute, Rockville, Maryland 20852, USA.
Stephen Chanock: Advanced Technology Center, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
Jolanta Lissowska: Cancer Center and M. Sklodowska‐Curie Institute of Oncology, Warsaw 02781, Poland.
Beata Peplonska: Nofer Institute of Occupational Medicine, Lodz 90950, Poland.
Heli Nevanlinna: and
Rainer Fagerholm: and
Hannaleena Eerola: and
Daehee Kang: Seoul National University College of Medicine, Seoul 151‐742, Korea.
Keun-Young Yoo: Seoul National University College of Medicine, Seoul 151‐742, Korea.
Dong-Young Noh: Seoul National University College of Medicine, Seoul 151‐742, Korea.
Sei-Hyun Ahn: Ulsan University College of Medicine, Ulsan 680‐749, Korea.
David J. Hunter: Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, Massachusetts 02115, USA.
Susan E. Hankinson: Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Ave., Boston, Massachusetts 02115, USA.
David G. Cox: Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, Massachusetts 02115, USA.
Per Hall: Karolinska Institute, Stockholm SE‐171 77, Sweden.
Sara Wedren: Karolinska Institute, Stockholm SE‐171 77, Sweden.
Jianjun Liu: Population Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.
Yen-Ling Low: Population Genetics, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Republic of Singapore.
Natalia Bogdanova: Department of Radiation Oncology and
Peter Schürmann: Hannover Medical School, D‐30625 Hannover, Germany.
Thilo Dörk: Hannover Medical School, D‐30625 Hannover, Germany.
Rob A. E. M. Tollenaar: Department of Surgery and
Catharina E. Jacobi: Department of Medical Decision Making and
Peter Devilee: Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
Jan G. M. Klijn: Family Cancer Clinic, Erasmus MC‐Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands.
Alice J. Sigurdson: Radiation Epidemiology Branch, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.
Michele M. Doody: Radiation Epidemiology Branch, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA.
Bruce H. Alexander: Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Jinghui Zhang: Laboratory of Population Genetics, US National Cancer Institute, Bethesda, Maryland 20892, USA.
Angela Cox: Institute for Cancer Studies and
Ian W. Brock: Institute for Cancer Studies and
Gordon MacPherson: Institute for Cancer Studies and
Malcolm W. R. Reed: Academic Unit of Surgical Oncology, Sheffield University Medical School, Sheffield S10 2RX, UK.
Fergus J. Couch: Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Ellen L. Goode: Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Janet E. Olson: Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Hanne Meijers-Heijboer: VU University Medical Center, 1007 MB Amsterdam, the Netherlands.
Ans van den Ouweland: Department of Clinical Genetics and
André Uitterlinden: Internal Medicine, Erasmus University, Rotterdam NL‐3015‐GE, the Netherlands.
Fernando Rivadeneira: Internal Medicine, Erasmus University, Rotterdam NL‐3015‐GE, the Netherlands.
Roger L. Milne: Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.
Gloria Ribas: Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.
Anna Gonzalez-Neira: Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.
Javier Benitez: Spanish National Cancer Centre (CNIO), Madrid E‐28029, Spain.
John L. Hopper: Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Carlton, Victoria 3053, Australia.
Margaret McCredie: University of Otago, Dunedin 9001, New Zealand.
Melissa Southey: Centre for Molecular, Environmental, Genetic and Analytical Epidemiology, University of Melbourne, Carlton, Victoria 3053, Australia.
Graham G. Giles: Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria 3053, Australia.
Chris Schroen: Genetic Epidemiology Laboratory, University of Melbourne, Parkville, Victoria 3052, Australia.
Christina Justenhoven: Dr. Margarete Fischer‐Bosch‐Institute of Clinical Pharamcology, 70376 Stuttgart and University of Tuebingen, 72074 Tuebingen, Germany.
Hiltrud Brauch: Dr. Margarete Fischer‐Bosch‐Institute of Clinical Pharamcology, 70376 Stuttgart and University of Tuebingen, 72074 Tuebingen, Germany.
Ute Hamann: Deutsches Krebsforschungszentrum, Heidelberg 69120, Germany.
Yon-Dschun Ko: Evangelische Kliniken Bonn gGmbH Johanniter Krankenhaus, 53113 Bonn, Germany.
Amanda B. Spurdle: Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
Jonathan Beesley: Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
Xiaoqing Chen: Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
Arto Mannermaa: Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Veli-Matti Kosma: Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Vesa Kataja: Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Jaana Hartikainen: Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia.
Nicholas E. Day: Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.
David R. Cox: Genetic Health Services Victoria, Royal Children’s Hospital, Melbourne, Victoria 3050, Australia.
Bruce A. J. Ponder: Oncology Research Centre, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.

Nature, 2007, vol. 447, issue 7148, 1087-1093

Abstract: 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

Date: 2007
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DOI: 10.1038/nature05887

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