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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Zeng C 1 , Guo X 1 , Long J 1 , Kuchenbaecker KB 2 , Droit A 3 , Michailidou K 2 Show all authors , Ghoussaini M 4 , Kar S 4 , Freeman A 5 , Hopper JL 6 , Milne RL 6 , Bolla MK 2 , Wang Q 2 , Dennis J 2 , Agata S 7 , Ahmed S 8 , Aittomäki K 9 , Andrulis IL 10 , Anton-Culver H 11 , Antonenkova NN 12 , Arason A 13 , Arndt V 14 , Arun BK 15 , Arver B 16 , Bacot F 17 , Barrowdale D 2 , Baynes C 8 , Beeghly-Fadiel A 1 , Benitez J 18 , Bermisheva M 19 , Blomqvist C 20 , Blot WJ 1 , Bogdanova NV 21 , Bojesen SE 22 , Bonanni B 23 , Borresen-Dale AL 24 , Brand JS 25 , Brauch H 26 , Brennan P 27 , Brenner H 14 , Broeks A 28 , Brüning T 29 , Burwinkel B 30 , Buys SS 31 , Cai Q 1 , Caldes T 32 , Campbell I 33 , Carpenter J 34 , Chang-Claude J 35 , Choi JY 36 , Claes KB 37 , Clarke C 38 , Cox A 39 , Cross SS 40 , Czene K 25 , Daly MB 41 , de la Hoya M 32 , De Leeneer K 37 , Devilee P 42 , Diez O 43 , Domchek SM 44 , Doody M 45 , Dorfling CM 46 , Dörk T 47 , Dos-Santos-Silva I 48 , Dumont M 49 , Dwek M 50 , Dworniczak B 51 , Egan K 52 , Eilber U 35 , Einbeigi Z 53 , Ejlertsen B 54 , Ellis S 2 , Frost D 2 , Lalloo F 55 , EMBRACE , Fasching PA 56 , Figueroa J 45 , Flyger H 57 , Friedlander M 58 , Friedman E 59 , Gambino G 60 , Gao YT 61 , Garber J 62 , García-Closas M 45 , Gehrig A 63 , Damiola F 64 , Lesueur F 65 , Mazoyer S 64 , Stoppa-Lyonnet D 66 , behalf of GEMO Study Collaborators , Giles GG 6 , Godwin AK 67 , Goldgar DE 68 , González-Neira A 18 , Greene MH 69 , Guénel P 70 , Haeberle L 56 , Haiman CA 71 , Hallberg E 72 , Hamann U 73 , Hansen TV 74 , Hart S 72 , Hartikainen JM 75 , Hartman M 76 , Hassan N 77 , Healey S 78 , Hogervorst FB 79 , Verhoef S 79 , HEBON , Hendricks CB 80 , Hillemanns P 47 , Hollestelle A 81 , Hulick PJ 82 , Hunter DJ 83 , Imyanitov EN 84 , Isaacs C 85 , Ito H 86 , Jakubowska A 87 , Janavicius R 88 , Jaworska-Bieniek K 87 , Jensen UB 89 , John EM 90 , Joly Beauparlant C 91 , Jones M 92 , Kabisch M 73 , Kang D 36 , Karlan BY 93 , Kauppila S 94 , Kerin MJ 95 , Khan S 96 , Khusnutdinova E 19 , Knight JA 97 , Konstantopoulou I 98 , Kraft P 83 , Kwong A 99 , Laitman Y 59 , Lambrechts D 100 , Lazaro C 101 , Le Marchand L 102 , Lee CN 76 , Lee MH 103 , Lester J 93 , Li J 25 , Liljegren A 16 , Lindblom A 104 , Lophatananon A 105 , Lubinski J 87 , Mai PL 69 , Mannermaa A 75 , Manoukian S 106 , Margolin S 107 , Marme F 30 , Matsuo K 108 , McGuffog L 2 , Meindl A 109 , Menegaux F 70 , Montagna M 7 , Muir K 105 , Mulligan AM 110 , Nathanson KL 44 , Neuhausen SL 111 , Nevanlinna H 96 , Newcomb PA 112 , Nord S 24 , Nussbaum RL 113 , Offit K 114 , Olah E 115 , Olopade OI 116 , Olswold C 72 , Osorio A 117 , Papi L 118 , Park-Simon TW 47 , Paulsson-Karlsson Y 119 , Peeters S 120 , Peissel B 121 , Peterlongo P 122 , Peto J 48 , Pfeiler G 123 , Phelan CM 124 , Presneau N 50 , Radice P 125 , Rahman N 126 , Ramus SJ 127 , Rashid MU 73 , Rennert G 128 , Rhiem K 129 , Rudolph A 35 , Salani R 130 , Sangrajrang S 131 , Sawyer EJ 132 , Schmidt MK 28 , Schmutzler RK 133 , Schoemaker MJ 92 , Schürmann P 47 , Seynaeve C 81 , Shen CY 134 , Shrubsole MJ 1 , Shu XO 1 , Sigurdson A 45 , Singer CF 135 , Slager S 72 , Soucy P 136 , Southey M 137 , Steinemann D 138 , Swerdlow A 92 , Szabo CI 139 , Tchatchou S 140 , Teixeira MR 141 , Teo SH 77 , Terry MB 142 , Tessier DC 17 , Teulé A 143 , Thomassen M 144 , Tihomirova L 145 , Tischkowitz M 146 , Toland AE 147 , Tung N 148 , Turnbull C 126 , van den Ouweland AM 149 , van Rensburg EJ 46 , Ven den Berg D 71 , Vijai J 114 , Wang-Gohrke S 150 , Weitzel JN 151 , Whittemore AS 152 , Winqvist R 153 , Wong TY 154 , Wu AH 71 , Yannoukakos D 155 , Yu JC 156 , Pharoah PD 2 , Hall P 25 , Chenevix-Trench G 157 , KConFab , AOCS Investigators , Dunning AM 8 , Simard J 49 , Couch FJ 158 , Antoniou AC 2 , Easton DF 2 , Zheng W 159

Affiliations 

  • 1 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA
  • 2 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • 3 Proteomics Center, CHU de Québec Research Center and Department of Molecular Medicine, Laval University, Quebec, Canada
  • 4 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK
  • 5 Department of Surgery, St Vincent's Hospital, Melbourne, VIC, Australia
  • 6 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia
  • 7 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Padua, Italy
  • 8 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
  • 9 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 10 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
  • 11 Department of Epidemiology, University of California Irvine, Irvine, CA, USA
  • 12 N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
  • 13 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland
  • 14 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 15 University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • 16 Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
  • 17 McGill University and Génome Québec Innovation Centre, Montréal, Canada
  • 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
  • 19 Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia
  • 20 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 21 Department of Radiation Oncology, Hannover Medical School, Hannover, Germany
  • 22 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 23 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy
  • 24 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  • 25 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 26 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
  • 27 International Agency for Research on Cancer, Lyon, France
  • 28 Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
  • 29 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany
  • 30 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
  • 31 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
  • 32 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain
  • 33 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
  • 34 Australian Breast Cancer Tissue Bank, Westmead Millennium Institute, University of Sydney, Sydney, Australia
  • 35 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 36 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
  • 37 Center for Medical Genetics, Ghent University, Ghent, Belgium
  • 38 Westmead Millenium Institute for Medical Research, University of Sydney, Sydney, Australia
  • 39 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK
  • 40 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
  • 41 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA
  • 42 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
  • 43 Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain
  • 44 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • 45 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
  • 46 Department of Genetics, University of Pretoria, Pretoria, South Africa
  • 47 Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany
  • 48 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  • 49 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada
  • 50 Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK
  • 51 Institute of Human Genetics, Muenster, Germany
  • 52 Division of Population Sciences, Moffitt Cancer Center & Research Institute, Tampa, FL, USA
  • 53 Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 54 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 55 Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  • 56 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  • 57 Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 58 ANZ GOTG Coordinating Centre, Australia New Zealand GOG, Camperdown, NSW, Australia
  • 59 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel
  • 60 Section of Genetic Oncology, Deparment of Laboratory Medicine, University and University Hospital of Pisa, Pisa, Italy
  • 61 Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
  • 62 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA
  • 63 Institute of Human Genetics, University Würzburg, Wurzburg, Germany
  • 64 INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France
  • 65 Genetic Epidemiology of Cancer team, Inserm, U900, Institut Curie, Mines ParisTech, 75248, Paris, France
  • 66 Department of Tumour Biology, Institut Curie, Paris, France
  • 67 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA
  • 68 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
  • 69 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
  • 70 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France
  • 71 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 72 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
  • 73 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 74 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  • 75 Cancer Center, Kuopio University Hospital, Kuopio, Finland
  • 76 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 77 Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia
  • 78 Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  • 79 Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 80 Suburban Hospital, Bethesda, MD, USA
  • 81 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  • 82 Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA
  • 83 Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA, USA
  • 84 N.N. Petrov Institute of Oncology, St. Petersburg, Russia
  • 85 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
  • 86 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan
  • 87 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 88 State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
  • 89 Department of Clinical Genetics, Aarhus University Hospital, Aarhus, N, Denmark
  • 90 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA
  • 91 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, QC, Canada
  • 92 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
  • 93 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • 94 Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland
  • 95 School of Medicine, National University of Ireland, Galway, Ireland
  • 96 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 97 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
  • 98 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Athens, Greece
  • 99 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China
  • 100 Vesalius Research Center, Leuven, Belgium
  • 101 Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain
  • 102 University of Hawaii Cancer Center, Honolulu, HI, USA
  • 103 Department of Surgery, Soonchunhyang University and Hospital, Seoul, South Korea
  • 104 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  • 105 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
  • 106 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Milan, Italy
  • 107 Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden
  • 108 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
  • 109 Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany
  • 110 Laboratory Medicine Program, University Health Network, Toronto, ON, Canada
  • 111 Beckman Research Institute of City of Hope, Duarte, CA, USA
  • 112 Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
  • 113 Department of Medicine and Genetics, University of California, San Francisco, San Francisco, CA, USA
  • 114 Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  • 115 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  • 116 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL, USA
  • 117 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain
  • 118 Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
  • 119 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  • 120 University Hospital Gashuisberg, Leuven, Belgium
  • 121 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Milan, Italy
  • 122 IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy
  • 123 Department of Obstetrics and Gynecology, and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 124 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
  • 125 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Milan, Italy
  • 126 Section of Cancer Genetics, The Institute of Cancer Research, London, UK
  • 127 Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  • 128 Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Haifa, Israel
  • 129 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany
  • 130 Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA
  • 131 National Cancer Institute, Bangkok, Thailand
  • 132 Research Oncology, Guy's Hospital, King's College London, London, UK
  • 133 Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany
  • 134 School of Public Health, China Medical University, Taichung, Taiwan
  • 135 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • 136 Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, QC, Canada
  • 137 Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia
  • 138 Hannover Medical School, Hannover, Germany
  • 139 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
  • 140 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada
  • 141 Department of Genetics, Portuguese Oncology Institute, Porto, Portugal
  • 142 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
  • 143 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain
  • 144 Department of Clinical Genetics, Odense University Hospital, Odense, C, Denmark
  • 145 Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 146 Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, QC, Canada
  • 147 Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
  • 148 Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • 149 Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 150 Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany
  • 151 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA
  • 152 Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
  • 153 Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu, Finland
  • 154 Singapore Eye Research Institute, National University of Singapore, Singapore, Singapore
  • 155 Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece
  • 156 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
  • 157 Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 158 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 159 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA. wei.zheng@vanderbilt.edu
Breast Cancer Res, 2016 06 21;18(1):64.
PMID: 27459855 DOI: 10.1186/s13058-016-0718-0

Abstract

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.

RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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