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    Nature genetics. 2016 Feb 29. pii: ng.3521. doi: 10.1038/ng.3521
    Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.
    Dunning AM1,  Michailidou K2,  Kuchenbaecker KB3,  Thompson D4,  French JD5,  Beesley J6,  Healey CS7,  Kar S8,  Pooley KA9,  Lopez-Knowles E10,  Dicks E11,  Barrowdale D12,  Sinnott-Armstrong NA13,  Sallari RC14,  Hillman KM15,  Kaufmann S16,  Sivakumaran H17,  Marjaneh MM18,  Lee JS19,  Hills M20,  Jarosz M21,  Drury S22,  Canisius S23,  Bolla MK24,  Dennis J25,  Wang Q26,  Hopper JL27,  Southey MC28,  Broeks A29,  Schmidt MK30,  Lophatananon A31,  Muir K32,  Beckmann MW33,  Fasching PA34,  Dos-Santos-Silva I35,  Peto J36,  Sawyer EJ37,  Tomlinson I38,  Burwinkel B39,  Marme F40,  Guénel P41,  Truong T42,  Bojesen SE43,  Flyger H44,  González-Neira A45,  Perez JI46,  Anton-Culver H47,  Eunjung L48,  Arndt V49,  Brenner H50,  Meindl A51,  Schmutzler RK52,  Brauch H53,  Hamann U54,  Aittomäki K55,  Blomqvist C56,  Ito H57,  Matsuo K58,  Bogdanova N59,  Dörk T60,  Lindblom A61,  Margolin S62,  Kosma VM63,  Mannermaa A64,  Tseng CC65,  Wu AH66,  Lambrechts D67,  Wildiers H68,  Chang-Claude J69,  Rudolph A70,  Peterlongo P71,  Radice P72,  Olson JE73,  Giles GG74,  Milne RL75,  Haiman CA76,  Henderson BE77,  Goldberg MS78,  Teo SH79,  Yip CH80,  Nord S81,  Borresen-Dale AL82,  Kristensen V83,  Long J84,  Zheng W85,  Pylkäs K86,  Winqvist R87,  Andrulis IL88,  Knight JA89,  Devilee P90,  Seynaeve C91,  Figueroa J92,  Sherman ME93,  Czene K94,  Darabi H95,  Hollestelle A96,  van den Ouweland AM97,  Humphreys K98,  Gao YT99,  Shu XO100,  Cox A101,  Cross SS102,  Blot W103,  Cai Q104,  Ghoussaini M105,  Perkins BJ106,  Shah M107,  Choi JY108,  Kang D109,  Lee SC110,  Hartman M111,  Kabisch M112,  Torres D113,  Jakubowska A114,  Lubinski J115,  Brennan P116,  Sangrajrang S117,  Ambrosone CB118,  Toland AE119,  Shen CY120,  Wu PE121,  Orr N122,  Swerdlow A123,  McGuffog L124,  Healey S125,  Lee A126,  Kapuscinski M127,  John EM128,  Terry MB129,  Daly MB130,  Goldgar DE131,  Buys SS132,  Janavicius R133,  Tihomirova L134,  Tung N135,  Dorfling CM136,  van Rensburg EJ137,  Neuhausen SL138,  Ejlertsen B139,  Hansen TV140,  Osorio A141,  Benitez J142,  Rando R143,  Weitzel JN144,  Bonanni B145,  Peissel B146,  Manoukian S147,  Papi L148,  Ottini L149,  Konstantopoulou I150,  Apostolou P151,  Garber J152,  Rashid MU153,  Frost D154,  Izatt L155,  Ellis S156,  Godwin AK157,  Arnold N158,  Niederacher D159,  Rhiem K160,  Bogdanova-Markov N161,  Sagne C162,  Stoppa-Lyonnet D163,  Damiola F164,  Sinilnikova OM165,  Mazoyer S166,  Isaacs C167,  Claes KB168,  De Leeneer K169,  de la Hoya M170,  Caldes T171,  Nevanlinna H172,  Khan S173,  Mensenkamp AR174,  Hooning MJ175,  Rookus MA176,  Kwong A177,  Olah E178,  Diez O179,  Brunet J180,  Pujana MA181,  Gronwald J182,  Huzarski T183,  Barkardottir RB184,  Laframboise R185,  Soucy P186,  Montagna M187,  Agata S188,  Teixeira MR189,  Park SK190,  Lindor N191,  Couch FJ192,  Tischkowitz M193,  Foretova L194,  Vijai J195,  Offit K196,  Singer CF197,  Rappaport C198,  Phelan CM199,  Greene MH200,  Mai PL201,  Rennert G202,  Imyanitov EN203,  Hulick PJ204,  Phillips KA205,  Piedmonte M206,  Mulligan AM207,  Glendon G208,  Bojesen A209,  Thomassen M210,  Caligo MA211,  Yoon SY212,  Friedman E213,  Laitman Y214,  Borg A215,  von Wachenfeldt A216,  Ehrencrona H217,  Rantala J218,  Olopade OI219,  Ganz PA220,  Nussbaum RL221,  Gayther SA222,  Nathanson KL223,  Domchek SM224,  Arun BK225,  Mitchell G226,  Karlan BY227,  Lester J228,  Maskarinec G229,  Woolcott C230,  Scott C231,  Stone J232,  Apicella C233,  Tamimi R234,  Luben R235,  Khaw KT236,  Helland Å237,  Haakensen V238,  Dowsett M239,  Pharoah PD240,  Simard J241,  Hall P242,  García-Closas M243,  Vachon C244,  Chenevix-Trench G245,  Antoniou AC246,  Easton DF247,  Edwards SL248
    Author information
    1Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    2Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    3Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    4Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    5Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    6Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    7Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    8Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    9Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    10Breast Cancer Research, Breakthrough Breast Cancer Research Centre, London, UK.
    11Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    12Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    13Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
    14Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
    15Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    16Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    17Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    18Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    19Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    20Academic Biochemistry, Royal Marsden Hospital, London, UK.
    21Breast Cancer Research, Breakthrough Breast Cancer Research Centre, London, UK.
    22Breast Cancer Research, Breakthrough Breast Cancer Research Centre, London, UK.
    23Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
    24Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    25Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    26Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    27Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
    28Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
    29Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
    30Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
    31Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
    32Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
    33Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg Metropolitan Region, Erlangen, Germany.
    34Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Nuremberg Metropolitan Region, Erlangen, Germany.
    35Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
    36Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
    37Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London, UK.
    38Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
    39Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    40National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
    41Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
    42Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France.
    43Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
    44Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
    45Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.
    46Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
    47Department of Epidemiology, University of California-Irvine, Irvine, California, USA.
    48Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    49Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    50Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
    51Department of Gynaecology and Obstetrics, Technical University of Munich, Munich, Germany.
    52Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany.
    53German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
    54Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.
    55Department of Clinical Genetics, Helsinki University Central Hospital, Helsinki, Finland.
    56Department of Oncology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
    57Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
    58Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
    59Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany.
    60Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
    61Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    62Department of Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden.
    63Cancer Center, Kuopio University Hospital, Kuopio, Finland.
    64Cancer Center, Kuopio University Hospital, Kuopio, Finland.
    65Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    66Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    67Vesalius Research Center, Leuven, Belgium.
    68Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
    69Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    70Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    71IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
    72Unit of Molecular Basis of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    73Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    74Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
    75Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
    76Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    77Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    78Department of Medicine, McGill University, Montreal, Quebec, Canada.
    79Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.
    80Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
    81Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
    82Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
    83Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
    84Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    85Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    86Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu University Hospital, Oulu, Finland.
    87Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu University Hospital, Oulu, Finland.
    88Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
    89Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
    90Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
    91Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands.
    92Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
    93Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
    94Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    95Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    96Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands.
    97Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
    98Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    99Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
    100Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    101Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.
    102Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
    103Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    104Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
    105Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    106Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    107Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    108Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
    109Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
    110Department of Haematology-Oncology, National University Health System, Singapore.
    111Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
    112Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.
    113Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.
    114Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    115Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    116International Agency for Research on Cancer, Lyon, France.
    117National Cancer Institute, Bangkok, Thailand.
    118Roswell Park Cancer Institute, Buffalo, New York, USA.
    119Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
    120School of Public Health, China Medical University, Taichung, Taiwan.
    121Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
    122Division of Cancer Studies, Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
    123Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
    124Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    125Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    126Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    127Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia.
    128Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California, USA.
    129Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
    130Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
    131Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    132Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
    133State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
    134Latvian Biomedical Research and Study Centre, Riga, Latvia.
    135Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
    136Department of Genetics, University of Pretoria, Pretoria, South Africa.
    137Department of Genetics, University of Pretoria, Pretoria, South Africa.
    138Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California, USA.
    139Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    140Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    141Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
    142Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
    143City of Hope Clinical Cancer Genomics Community Research Network, Duarte, California, USA.
    144Clinical Cancer Genetics, City of Hope, Duarte, California, USA.
    145Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.
    146Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
    147Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy.
    148Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
    149Department of Molecular Medicine, University La Sapienza, Rome, Italy.
    150Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology), National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece.
    151Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology), National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece.
    152Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
    153Molecular Genetics of Breast Cancer, German Cancer Research Center, Heidelberg, Germany.
    154Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    155Clinical Genetics, Guy's and St. Thomas' National Health Service (NHS) Foundation Trust, London, UK.
    156Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    157Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
    158Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian Albrechts University Kiel, Kiel, Germany.
    159University Düsseldorf, Dusseldorf, Germany.
    160Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology, Center for Molecular Medicine Cologne, University Hospital of Cologne, Cologne, Germany.
    161Institute of Human Genetics, Münster, Germany.
    162INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
    163Institut Curie, Department of Tumour Biology, Paris, France.
    164INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
    165INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
    166INSERM U1052, CNRS UMR 5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
    167Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
    168Center for Medical Genetics, Ghent University, Ghent, Belgium.
    169Center for Medical Genetics, Ghent University, Ghent, Belgium.
    170Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.
    171Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.
    172Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
    173Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
    174Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
    175Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, the Netherlands.
    176Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
    177Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong.
    178Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
    179Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain.
    180Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona), Catalan Institute of Oncology, Girona, Spain.
    181Breast Cancer and Systems Biology Unit, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain.
    182Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    183Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
    184Department of Pathology, Landspitali University Hospital and Biomedical Centre (BMC), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    185Medical Genetic Division, Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada.
    186Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada.
    187Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV), IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Padua, Italy.
    188Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV), IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Padua, Italy.
    189Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
    190Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
    191Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    192Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    193Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada.
    194Masaryk Memorial Cancer Institute and Medical Faculty, Masaryk University, Brno, Czech Republic.
    195Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
    196Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
    197Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
    198Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
    199Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
    200Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Rockville, Maryland, USA.
    201Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Rockville, Maryland, USA.
    202Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Haifa, Israel.
    203N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
    204Center for Medical Genetics, NorthShore University Health System, Evanston, Illinois, USA.
    205Division of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
    206NRG Oncology, Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, New York, USA.
    207Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada.
    208Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
    209Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
    210Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
    211Section of Genetic Oncology, Department of Laboratory Medicine, University of Pisa and University Hospital of Pisa, Pisa, Italy.
    212Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia.
    213Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.
    214Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.
    215Department of Oncology, Lund University, Lund, Sweden.
    216Department of Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden.
    217Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    218Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
    219Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois, USA.
    220Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center, University of California Los Angeles School of Medicine and School of Public Health, Los Angeles, California, USA.
    221Department of Medicine and Genetics, University of California, San Francisco, San Francisco, California, USA.
    222Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
    223Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
    224Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
    225University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
    226Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
    227Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
    228Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
    229University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
    230Department of Obstetrics, Gynaecology and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
    231Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    232Centre for Genetic Origins of Health and Disease, University of Western Australia, Perth, Western Australia, Australia.
    233Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
    234Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
    235Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    236Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    237Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
    238Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
    239Breast Cancer Research, Breakthrough Breast Cancer Research Centre, London, UK.
    240Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    241Centre Hospitalier Universitaire de Québec and Laval University, Quebec City, Quebec, Canada.
    242Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    243Division of Cancer Studies, Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
    244Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
    245Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    246Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
    247Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
    248Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
    Abstract

    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.


    Publikations ID: 26928228
    Quelle: öffnen
     
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