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    Nature communications. 2016 Apr 27. pii: ncomms11375. doi: 10.1038/ncomms11375
    Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.
    Couch FJ1,  Kuchenbaecker KB2,  Michailidou K3,  Mendoza-Fandino GA4,  Nord S5,  Lilyquist J6,  Olswold C7,  Hallberg E8,  Agata S9,  Ahsan H10,  Aittomäki K11,  Ambrosone C12,  Andrulis IL13,  Anton-Culver H14,  Arndt V15,  Arun BK16,  Arver B17,  Barile M18,  Barkardottir RB19,  Barrowdale D20,  Beckmann L21,  Beckmann MW22,  Benitez J23,  Blank SV24,  Blomqvist C25,  Bogdanova NV26,  Bojesen SE27,  Bolla MK28,  Bonanni B29,  Brauch H30,  Brenner H31,  Burwinkel B32,  Buys SS33,  Caldes T34,  Caligo MA35,  Canzian F36,  Carpenter J37,  Chang-Claude J38,  Chanock SJ39,  Chung WK40,  Claes KB41,  Cox A42,  Cross SS43,  Cunningham JM44,  Czene K45,  Daly MB46,  Damiola F47,  Darabi H48,  de la Hoya M49,  Devilee P50,  Diez O51,  Ding YC52,  Dolcetti R53,  Domchek SM54,  Dorfling CM55,  Dos-Santos-Silva I56,  Dumont M57,  Dunning AM58,  Eccles DM59,  Ehrencrona H60,  Ekici AB61,  Eliassen H62,  Ellis S63,  Fasching PA64,  Figueroa J65,  Flesch-Janys D66,  Försti A67,  Fostira F68,  Foulkes WD69,  Friebel T70,  Friedman E71,  Frost D72,  Gabrielson M73,  Gammon MD74,  Ganz PA75,  Gapstur SM76,  Garber J77,  Gaudet MM78,  Gayther SA79,  Gerdes AM80,  Ghoussaini M81,  Giles GG82,  Glendon G83,  Godwin AK84,  Goldberg MS85,  Goldgar DE86,  González-Neira A87,  Greene MH88,  Gronwald J89,  Guénel P90,  Gunter M91,  Haeberle L92,  Haiman CA93,  Hamann U94,  Hansen TV95,  Hart S96,  Healey S97,  Heikkinen T98,  Henderson BE99,  Herzog J100,  Hogervorst FB101,  Hollestelle A102,  Hooning MJ103,  Hoover RN104,  Hopper JL105,  Humphreys K106,  Hunter DJ107,  Huzarski T108,  Imyanitov EN109,  Isaacs C110,  Jakubowska A111,  James P112,  Janavicius R113,  Jensen UB114,  John EM115,  Jones M116,  Kabisch M117,  Kar S118,  Karlan BY119,  Khan S120,  Khaw KT121,  Kibriya MG122,  Knight JA123,  Ko YD124,  Konstantopoulou I125,  Kosma VM126,  Kristensen V127,  Kwong A128,  Laitman Y129,  Lambrechts D130,  Lazaro C131,  Lee E132,  Le Marchand L133,  Lester J134,  Lindblom A135,  Lindor N136,  Lindstrom S137,  Liu J138,  Long J139,  Lubinski J140,  Mai PL141,  Makalic E142,  Malone KE143,  Mannermaa A144,  Manoukian S145,  Margolin S146,  Marme F147,  Martens JW148,  McGuffog L149,  Meindl A150,  Miller A151,  Milne RL152,  Miron P153,  Montagna M154,  Mazoyer S155,  Mulligan AM156,  Muranen TA157,  Nathanson KL158,  Neuhausen SL159,  Nevanlinna H160,  Nordestgaard BG161,  Nussbaum RL162,  Offit K163,  Olah E164,  Olopade OI165,  Olson JE166,  Osorio A167,  Park SK168,  Peeters PH169,  Peissel B170,  Peterlongo P171,  Peto J172,  Phelan CM173,  Pilarski R174,  Poppe B175,  Pylkäs K176,  Radice P177,  Rahman N178,  Rantala J179,  Rappaport C180,  Rennert G181,  Richardson A182,  Robson M183,  Romieu I184,  Rudolph A185,  Rutgers EJ186,  Sanchez MJ187,  Santella RM188,  Sawyer EJ189,  Schmidt DF190,  Schmidt MK191,  Schmutzler RK192,  Schumacher F193,  Scott R194,  Senter L195,  Sharma P196,  Simard J197,  Singer CF198,  Sinilnikova OM199,  Soucy P200,  Southey M201,  Steinemann D202,  Stenmark-Askmalm M203,  Stoppa-Lyonnet D204,  Swerdlow A205,  Szabo CI206,  Tamimi R207,  Tapper W208,  Teixeira MR209,  Teo SH210,  Terry MB211,  Thomassen M212,  Thompson D213,  Tihomirova L214,  Toland AE215,  Tollenaar RA216,  Tomlinson I217,  Truong T218,  Tsimiklis H219,  Teulé A220,  Tumino R221,  Tung N222,  Turnbull C223,  Ursin G224,  van Deurzen CH225,  van Rensburg EJ226,  Varon-Mateeva R227,  Wang Z228,  Wang-Gohrke S229,  Weiderpass E230,  Weitzel JN231,  Whittemore A232,  Wildiers H233,  Winqvist R234,  Yang XR235,  Yannoukakos D236,  Yao S237,  Zamora MP238,  Zheng W239,  Hall P240,  Kraft P241,  Vachon C242,  Slager S243,  Chenevix-Trench G244,  Pharoah PD245,  Monteiro AA246,  García-Closas M247,  Easton DF248,  Antoniou AC249
    Author information
    1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
    2Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    4Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
    5Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, N-0310 Oslo, Norway.
    6Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    7Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    8Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    9Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, 20133 Padua, Italy.
    10Department of Health Studies, The University of Chicago, Chicago, Illinois 60637, USA.
    11Department of Clinical Genetics, Helsinki University Central Hospital, 00029 Helsinki, Finland.
    12Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
    13Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
    14Department of Epidemiology, University of California Irvine, Irvine, California, 92697, USA.
    15Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    16University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
    17Department of Oncology, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
    18Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, 20141 Milan, Italy.
    19Department of Pathology, Landspitali University Hospital and University of Iceland School of Medicine, 101 Reykjavik, Iceland.
    20Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    21Institute for Quality and Efficiency in Health Care (IQWiG), 50670 Cologne, Germany.
    22University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
    23Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain.
    24NYU Women's Cancer Program, New York University School of Medicine, New York, New York 10016, USA.
    25Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
    26Department of Radiation Oncology, Hannover Medical School, 30625 Hannover, Germany.
    27Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
    28Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    29Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, 20141 Milan, Italy.
    30Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.
    31Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    32Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany.
    33Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City Utah 84112, USA.
    34Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid 28040, Spain.
    35Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, I-56126 Pisa, Italy.
    36Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    37Australian Breast Cancer Tissue Bank, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
    38Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    39Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20850, USA.
    40Departments of Pediatrics and Medicine, Columbia University, New York, New York 10032, USA.
    41Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
    42Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK.
    43Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
    44Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
    45Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    46Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
    47INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France.
    48Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    49Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC, Madrid 28040, Spain.
    50Department of Human Genetics and Department of Pathology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
    51Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, 08035 Barcelona, Spain.
    52Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
    53Cancer Bioimmunotherapy Unit, CRO Aviano National Cancer Institute, 33081 Aviano , Italy.
    54Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Pennsylvania 19104, USA.
    55Department of Genetics, University of Pretoria, Pretoria 0007, South Africa.
    56Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
    57Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada G1V 4G2.
    58Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
    59Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, Hampshire SO16 6YD, UK.
    60Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751 85, Sweden.
    61Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
    62Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
    63Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    64University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
    65Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20850, USA.
    66Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, 20246 Hamburg, Germany.
    67Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    68Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece.
    69Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada H3A 0G4.
    70University of, Philadelphia, Pennsylvania 19104, USA.
    71Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel.
    72Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    73Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    74Department of Epidemiology, University of, Chapel Hill, North Carolina 27599-7400, USA.
    75UCLA Schools of Medicine and Public Health, Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-6900, USA.
    76Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
    77Cancer Risk and Prevention Clinic, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA.
    78Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
    79Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, California 90048, USA.
    80Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
    81Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
    82Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3010, Australia.
    83Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
    84Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, 66205, USA.
    85Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 2M1.
    86Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
    87Human Genotyping-CEGEN Unit, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
    88Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-9772, USA.
    89Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    90Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, 70-115 Villejuif, France.
    91Department of of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK.
    92University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
    93Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
    94Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    95Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.
    96Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    97Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
    98Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany.
    99Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
    100Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California 91010, USA.
    101Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam 1000 BE, The Netherlands.
    102Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam 3008 AE, The Netherlands.
    103Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3008 AE, The Netherlands.
    104Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20850, USA.
    105Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
    106Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    107Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
    108Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    109N.N. Petrov Institute of Oncology, 197758 St Petersburg, Russia.
    110Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
    111Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    112Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria 8006, Australia.
    113State Research Institute Centre for Innovative Medicine, LT-08661 Vilnius, Lithuania.
    114Department of Clinical Genetics, Aarhus University Hospital, 8200 Aarhus N, Denmark.
    115Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA.
    116Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton SM2 5NG, UK.
    117Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    118Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
    119Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
    120Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
    121Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
    122Department of Health Studies, The University of Chicago, Chicago, Illinois 60637, USA.
    123Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
    124Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, 53113 Bonn, Germany.
    125Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece.
    126School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
    127Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, N-0310 Oslo, Norway.
    128The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong.
    129Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel.
    130Vesalius Research Center, VIB, 3000 Leuven, Belgium.
    131Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain.
    132Department of Preventive Medicine, University of Southern California, Los Angeles, California 90032, USA.
    133Cancer Epidemiology Program, University of Cancer Center, Honolulu, Hawaii 96813, USA.
    134Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA.
    135Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    136Health Sciences Research, Mayo Clinic, Scotsdale, Arizona 85259, USA.
    137Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
    138Human Genetics Division, Genome Institute of Singapore, Singapore 138672, Singapore.
    139Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
    140Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    141Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850-9772, USA.
    142Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
    143Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
    144School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
    145Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy.
    146Department of Oncology, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
    147Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany.
    148Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam 3008 AE, The Netherlands.
    149Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    150Department of Gynaecology and Obstetrics, Technical University of Munich, 81675 Munich, Germany.
    151NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
    152Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3010, Australia.
    153Department of Genomics and Genome Sciences, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA.
    154Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV-IRCCS, 20133 Padua, Italy.
    155INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France.
    156Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada M5B 1W8.
    157Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, Germany.
    158Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Pennsylvania 19104, USA.
    159Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA.
    160Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, FI-00029 Helsinki, Finland.
    161Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
    162Invitae Corporation, San Francisco, California 94107, USA.
    163Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
    164Department of Molecular Genetics, National Institute of Oncology, H-1122 Budapest, Hungary.
    165Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA.
    166Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    167Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28029 Madrid, Spain.
    168Department of Preventive Medicine and Biomedical Science, Seoul National University College of Medicine and Cancer Research Institute, Seoul National University, 110-799 Seoul, Republic of Korea.
    169Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3508 GA, The Netherlands.
    170Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy.
    171IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20133 Milan, Italy.
    172Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
    173Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
    174Divison of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
    175Center for Medical Genetics, Ghent University, 9000 Ghent, Belgium.
    176Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, FI-90220 Oulu, Finland.
    177Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), 20133 Milan, Italy.
    178Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK.
    179Department of Clinical Genetics, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
    180Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, A 1090 Vienna, Austria.
    181Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Haifa 34362, Israel.
    182Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA.
    183Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
    184International Agency for Research on Cancer, 69008 Lyon, France.
    185Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
    186Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam 1006 BE, The Netherlands.
    187Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18014 Granada, Spain.
    188Department of Environmental Health Sciences, Columbia University, New York, New York, 10032, USA.
    189Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London SE1 9RT, UK.
    190Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
    191Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam 1006 BE, The Netherlands.
    192Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, University Hospital Cologne, Cologne 50931, Germany.
    193Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
    194Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales 2305, Australia.
    195Divison of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
    196Department of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas 66205, USA.
    197Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec City, Quebec, Canada G1V 4G2.
    198Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, A 1090 Vienna, Austria.
    199INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France.
    200Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec City, Quebec, Canada G1V 4G2.
    201Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
    202Hannover Medical School, 30625 Hannover, Germany.
    203Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, SE-58185 Linköping, Sweden.
    204Institut Curie, Department of Tumour Biology, 75248 Paris, France.
    205Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton SM2 5NG, UK.
    206National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-2152, USA.
    207Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
    208Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, Hampshire SO16 6YD, UK.
    209Department of Genetics, Portuguese Oncology Institute, Porto, 4200-072, Portugal.
    210Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya 47500, Malaysia.
    211Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, 10032, USA.
    212Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark.
    213Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    214Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia.
    215Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, 43210, USA.
    216Department of Surgical Oncology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands.
    217Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK.
    218Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, 70-115 Villejuif, France.
    219Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
    220Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, 08908 Barcelona, Spain.
    221Cancer Registry and Histopathology Unit, 'Civic-M.P. Arezzo' Hospital, 97100 ASP Ragusa, Italy.
    222Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, USA.
    223Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, UK.
    224Cancer Registry of Norway, Institute of Population-Based Cancer Research, N-0304 Oslo, Norway.
    225Department of Pathology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam 3000 CA, The Netherlands.
    226Department of Genetics, University of Pretoria, Pretoria 0007, South Africa.
    227Institute of Human Genetics, Charite Berlin, 13353 Berlin, Germany.
    228Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
    229University Hospital Ulm, 89075 Ulm, , Germany.
    230Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    231Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, California 91010, USA.
    232Department of Health Research and Policy-Epidemiology, Stanford University School of Medicine, Stanford, California 94305, USA.
    233Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals, B-3000 Leuven, Belgium.
    234Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, FI-90220 Oulu, Finland.
    235Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
    236Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, 15310 Athens, Greece.
    237Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
    238Servicio de Oncología Médica, Hospital Universitario La Paz, 28046 Madrid, Spain.
    239Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
    240Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
    241Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
    242Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    243Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
    244Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
    245Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
    246Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
    247Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA.
    248Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    249Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
    Abstract

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.


    Publikations ID: 27117709
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