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      • Record: found
      • Abstract: found
      • Article: found

      Association analysis identifies 65 new breast cancer risk loci

      research-article
      Author(s): 1 , 2 , 4 , 5 , 1 , 6 , 7 , 8 , 9 , 9 , 6 , 7 , 1 , 1 , 8 , 8 , 1 , 10 , 11 , 1 , 12 , 13 , 6 , 6 , 8 , 6 , 14 , 8 , 15 , 5 , 5 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 13 , 8 , 29 , 13 , 30 , 31 , 32 , 33 , 34 , 22 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 23 , 45 , 47 , 48 , 49 , 50 , 12 , 51 , 52 , 53 , 54 , 55 , 56 , 23 , 57 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 35 , 70 , NBCS Collaborators 41 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 8 , 86 , 12 , 87 , 88 , 50 , 89 , 90 , 42 , 91 , 92 , 93 , 17 , 36 , 94 , 9 , 95 , 96 , 97 , 96 , 98 , 99 , 100 , 49 , 101 , 102 , 103 , 104 , 42 , 29 , 105 , 48 , 106 , 107 , 108 , 109 , 110 , 111 , 46 , 42 , 60 , 112 , 113 , 62 , 58 , 62 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 30 , 41 , 121 , 122 , 123 , 86 , 29 , 124 , 125 , 126 , 127 , 128 , 129 , 28 , 130 , 8 , 131 , 132 , 133 , 134 , 67 , 135 , 29 , 136 , 11 , 36 , 65 , 137 , 137 , 48 , 116 , 138 , 139 , 129 , 42 , 140 , 141 , 140 , 141 , 142 , 143 , 122 , 144 , 145 , 146 , 147 , 109 , 11 , 148 , 149 , 13 , 129 , 122 , 68 , 69 , 150 , 151 , 152 , 153 , 32 , 102 , 153 , 154 , 155 , 156 , 132 , 133 , 134 , 41 , 77 , 78 , 49 , 64 , 157 , 158 , 159 , 160 , 161 , 127 , 162 , 163 , 135 , 164 , 165 , 42 , 131 , 166 , 167 , 43 , 44 , 168 , 57 , 169 , 170 , 122 , 8 , 29 , 64 , 65 , 115 , 116 , 95 , 96 , 116 , 171 , 172 , 132 , 133 , 134 , 173 , 100 , 174 , 175 , 176 , 112 , 177 , 141 , 178 , 114 , 46 , 179 , 18 , 180 , 181 , 182 , 90 , 67 , 152 , 183 , 169 , 170 , 184 , 185 , 186 , 33 , 153 , 187 , 37 , 38 , 188 , 37 , 38 , 39 , 131 , 189 , 131 , 49 , 131 , 109 , 190 , 68 , 69 , 150 , 36 , 191 , 192 , 193 , 94 , 116 , 194 , 195 , 196 , 165 , 172 , 26 , 97 , 102 , 17 , 197 , 198 , 199 , 200 , 201 , 165 , 165 , 8 , 58 , 202 , 17 , 203 , 204 , 13 , 29 , 205 , 206 , 207 , 208 , 209 , 116 , 124 , 125 , 126 , 55 , 210 , 148 , 211 , 36 , 212 , 213 , 131 , 201 , 137 , 8 , 214 , 215 , 216 , 127 , 217 , 57 , 57 , 187 , 210 , 218 , 219 , 220 , 221 , 169 , 191 , 222 , 127 , 55 , 56 , 148 , 223 , 5 , 99 , 100 , 207 , 224 , 132 , 225 , 226 , 176 , 183 , 227 , 28 , 228 , 108 , 229 , 230 , 19 , 129 , 231 , 86 , 127 , 232 , 233 , 234 , 235 , 236 , 131 , 237 , 127 , 85 , 238 , 239 , 28 , 90 , 18 , 240 , 241 , 175 , 146 , 147 , 187 , 100 , 242 , 197 , 198 , 128 , 127 , 127 , 142 , 48 , 243 , 244 , 245 , 246 , 57 , 247 , 11 , 21 , 248 , ABCTB Investigators 249 , kConFab/AOCS Investigators 194 , 250 , 14 , 251 , 1 , 9 , 117 , 252 , 253 , 90 , 1 , 8 , 13 , 254 , 42 , 255 , 5 , 100 , 115 , 116 , 48 , 12 , 256 , 48 , 8 , 6 , 7 , 6 , 9 , 5 , 100 , 1 , 8
      Publication date (Electronic):
      Journal: Nature

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry 1. We identified 65 new loci associated with overall breast cancer at p<5x10 -8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention.

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          Most cited references77

          • Record: found
          • Abstract: found
          • Article: not found

          Gene Ontology: tool for the unification of biology

          Michael Ashburner, Catherine A. Ball, Judith Blake … (2002)
          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
          Article 0 comments Cited 16254 times – based on 0 reviews     Review now
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            • Abstract: found
            • Article: not found

            Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

            A. Subramanian, P Tamayo, V K Mootha … (2005)
            Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.
            Article 0 comments Cited 14779 times – based on 0 reviews     Review now
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              • Record: found
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              • Article: not found

              Cytoscape: a software environment for integrated models of biomolecular interaction networks.

              Paul Shannon, Andrew Markiel, Owen Ozier … (2003)
              Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
              Article 0 comments Cited 12759 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0410462
                Journal ID (pubmed-jr-id): 6011
                Journal ID (nlm-ta): Nature
                Journal ID (iso-abbrev): Nature
                Title: Nature
                ISSN (Print): 0028-0836
                ISSN (Electronic): 1476-4687
                Publication date Nihms-submitted: 1 November 2017
                Publication date (Electronic): 23 October 2017
                Publication date (Print): 02 November 2017
                Publication date PMC-release: 23 April 2018
                Volume: 551
                Issue: 7678
                Pages: 92-94
                Affiliations
                [1 ]Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
                [2 ]Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
                [4 ]Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA
                [5 ]Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [6 ]Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
                [7 ]The Donnelly Centre, University of Toronto, Toronto, ON, Canada
                [8 ]Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
                [9 ]Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, QC, Canada
                [10 ]Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA
                [11 ]Cancer Genomics Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
                [12 ]Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
                [13 ]Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [14 ]UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia
                [15 ]Cancer Research UK Cambridge Research Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK
                [16 ]Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA
                [17 ]Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
                [18 ]Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands
                [19 ]Center for Cancer Epidemiology and Prevention, The University of Chicago, Chicago, IL, USA
                [20 ]Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
                [21 ]Department of Epidemiology, University of California Irvine, Irvine, CA, USA
                [22 ]N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
                [23 ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [24 ]Department of Public Health Sciences, and Cancer Research Institute, Queen’s University, Kingston, ON, Canada
                [25 ]Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
                [26 ]Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [27 ]Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA
                [28 ]McGill University and Génome Québec Innovation Centre, Montréal, QC, Canada
                [29 ]Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
                [30 ]Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
                [31 ]Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain
                [32 ]Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia
                [33 ]Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
                [34 ]Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
                [35 ]Department of Radiation Oncology, Hannover Medical School, Hannover, Germany
                [36 ]Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
                [37 ]Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
                [38 ]Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
                [39 ]Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [40 ]Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy
                [41 ]Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
                [42 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [43 ]Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
                [44 ]University of Tübingen, Tübingen, Germany
                [45 ]German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
                [46 ]International Agency for Research on Cancer, Lyon, France
                [47 ]Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
                [48 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
                [49 ]Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden
                [50 ]Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
                [51 ]Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada
                [52 ]Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
                [53 ]Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany
                [54 ]Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany
                [55 ]Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
                [56 ]Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [57 ]Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
                [58 ]Medical Oncology Department, Hospital Clínico San Carlos, IdISSC (Centro Investigacion Biomedica en Red), CIBERONC (Instituto de Investigación Sanitaria San Carlos), Madrid, Spain
                [59 ]Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [60 ]Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago De Compostela, Spain
                [61 ]Centro de Investigación en Red de Enfermedades Raras (CIBERER) y Centro Nacional de Genotipado (CEGEN-PRB2), Universidad de Santiago de Compostela, Santiago De Compostela, Spain
                [62 ]Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
                [63 ]Oncology and Genetics Unit, Instituto de Investigacion Biomedica (IBI) Orense-Pontevedra-Vigo, Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain
                [64 ]Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong
                [65 ]Department of Pathology, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
                [66 ]Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA
                [67 ]Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
                [68 ]Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea
                [69 ]Cancer Research Institute, Seoul National University, Seoul, Korea
                [70 ]Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
                [71 ]Department of Oncology, Haukeland University Hospital, Bergen, Norway
                [72 ]Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
                [73 ]Department of Pathology, Akershus University Hospital, Lørenskog, Norway
                [74 ]Department of Breast-Endocrine Surgery, Akershus University Hospital, Lørenskog, Norway
                [75 ]Department of Breast and Endocrine Surgery, Oslo University Hospital, Ullevål, Oslo, Norway
                [76 ]Department of Research, Vestre Viken, Drammen, Norway
                [77 ]Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
                [78 ]Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway
                [79 ]National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital Radiumhospitalet, Oslo, Norway
                [80 ]Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway
                [81 ]Department of Radiology and Nuclear Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway
                [82 ]Oslo University Hospital, Oslo, Norway
                [83 ]Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
                [84 ]Department of Oncology, Oslo University Hospital Ullevål, Oslo, Norway
                [85 ]Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
                [86 ]Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
                [87 ]Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
                [88 ]INSERM U1052, Cancer Research Center of Lyon, Lyon, France
                [89 ]Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
                [90 ]Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
                [91 ]Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA
                [92 ]Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
                [93 ]Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
                [94 ]Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
                [95 ]Southampton Clinical Trials Unit, Faculty of Medicine , University of Southampton, Southampton, UK
                [96 ]Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
                [97 ]Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK
                [98 ]Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
                [99 ]Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
                [100 ]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [101 ]Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
                [102 ]Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia
                [103 ]Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
                [104 ]LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany
                [105 ]David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA
                [106 ]Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK
                [107 ]Institute for Medical Biometrics and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [108 ]Department of Cancer Epidemiology, Clinical Cancer Registry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [109 ]Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK
                [110 ]Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
                [111 ]School of Public Health, Curtin University, Perth, Australia
                [112 ]Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
                [113 ]Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
                [114 ]Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece
                [115 ]Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia
                [116 ]Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
                [117 ]Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada
                [118 ]Department of Medicine, McGill University, Montréal, QC, Canada
                [119 ]Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, QC, Canada
                [120 ]Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
                [121 ]Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
                [122 ]Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
                [123 ]Centre de Recherche du Centre Hospitalier de Université de Montréal (CHUM), Université de Montréal, Montréal, QC, Canada
                [124 ]Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany
                [125 ]Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany
                [126 ]Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
                [127 ]Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
                [128 ]Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [129 ]Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [130 ]Department of Biostatistics & Epidemiology, University of Massachusetts, Amherst, Amherst, MA, USA
                [131 ]Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
                [132 ]Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
                [133 ]Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland
                [134 ]Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
                [135 ]Department of Surgery, National University Health System, Singapore, Singapore
                [136 ]School of Population Health, University of Western Australia, Perth, Australia
                [137 ]Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
                [138 ]Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
                [139 ]Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
                [140 ]Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
                [141 ]Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [142 ]Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
                [143 ]Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
                [144 ]Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany
                [145 ]Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA
                [146 ]Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA
                [147 ]Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
                [148 ]Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
                [149 ]Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
                [150 ]Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea
                [151 ]Department of Surgery, Nagano Matsushiro General Hospital, Nagano, Japan
                [152 ]School of Medicine, National University of Ireland, Galway, Ireland
                [153 ]Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
                [154 ]Department of Surgery, Daerim Saint Mary's Hospital, Seoul, Korea
                [155 ]Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada
                [156 ]Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
                [157 ]Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong
                [158 ]Department of Surgery, Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong
                [159 ]Vesalius Research Center, VIB, Leuven, Belgium
                [160 ]Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium
                [161 ]University of Hawaii Cancer Center, Honolulu, HI, USA
                [162 ]Department of Surgery, Soonchunhyang University College of Medicine and Soonchunhyang University Hospital, Seoul, Korea
                [163 ]Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, Korea
                [164 ]Department of Cardiac, Thoracic and Vascular Surgery, National University Health System, Singapore, Singapore
                [165 ]Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel
                [166 ]Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [167 ]Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland
                [168 ]German Breast Group, GmbH, Neu Isenburg, Germany
                [169 ]Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
                [170 ]Institute of Population Health, University of Manchester, Manchester, UK
                [171 ]Division of Public Health Sciences, Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [172 ]Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov" , Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia
                [173 ]Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy
                [174 ]Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
                [175 ]Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden
                [176 ]Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
                [177 ]Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
                [178 ]Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan
                [179 ]Anatomical Pathology, The Alfred Hospital, Melbourne, Australia
                [180 ]Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany
                [181 ]Servicio de Anatomía Patológica, Hospital Monte Naranco, Oviedo, Spain
                [182 ]Gynaecological Cancer Research Centre, Department for Women’s Cancer, Institute for Women's Health, University College London, London, UK
                [183 ]Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia
                [184 ]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
                [185 ]Laboratory Medicine Program, University Health Network, Toronto, ON, Canada
                [186 ]Université Paris Sorbonne Cité, INSERM UMR-S1147, Paris, France
                [187 ]Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
                [188 ]Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
                [189 ]Center for Clinical Cancer Genetics and Global Health, The University of Chicago, Chicago, IL, USA
                [190 ]University of New Mexico Health Sciences Center, University of New Mexico, Albuquerque, NM, USA
                [191 ]The Curtin UWA Centre for Genetic Origins of Health and Disease, Curtin University and University of Western Australia, Perth, Australia
                [192 ]Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain
                [193 ]IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy
                [194 ]Peter MacCallum Cancer Center, Melbourne, Australia
                [195 ]Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia
                [196 ]Department of Medicine, St Vincent’s Hospital, The University of Melbourne, Fitzroy, Australia
                [197 ]Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland
                [198 ]Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland
                [199 ]Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich, Munich, Germany
                [200 ]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 dei Tumori (INT), Milan, Italy
                [201 ]Section of Cancer Genetics, The Institute of Cancer Research, London, UK
                [202 ]Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain
                [203 ]Department of Oncology, Mayo Clinic, Rochester, MN, USA
                [204 ]Institute of Pathology, Staedtisches Klinikum Karlsruhe, Karlsruhe, Germany
                [205 ]Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands
                [206 ]Hereditary Cancer Clinic, University Hospital of Heraklion, Heraklion, Greece
                [207 ]Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
                [208 ]National Cancer Institute, Bangkok, Thailand
                [209 ]Research Oncology, Guy’s Hospital, King's College London, London, UK
                [210 ]National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
                [211 ]Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
                [212 ]Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, Australia
                [213 ]Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, Australia
                [214 ]Department of Medicine, Kansas University Medicial Center, Kansas City, KS, USA
                [215 ]School of Public Health, China Medical University, Taichung, Taiwan
                [216 ]Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
                [217 ]Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA
                [218 ]Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia
                [219 ]Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada
                [220 ]School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
                [221 ]Saarland Cancer Registry, Saarbrücken, Germany
                [222 ]Department of Obstetrics and Gynaecology, University of Melbourne and the Royal Women's Hospital, Melbourne, Australia
                [223 ]Division of Breast Cancer Research, The Institute of Cancer Research, London, UK
                [224 ]Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
                [225 ]Cancer Center, Kuopio University Hospital, Kuopio, Finland
                [226 ]Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland
                [227 ]Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
                [228 ]National Cancer Institute, Ministry of Public Health, Nonthaburi, Thailand
                [229 ]Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
                [230 ]Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
                [231 ]Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia
                [232 ]Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
                [233 ]Frauenklinik der Stadtklinik Baden-Baden, Baden-Baden, Germany
                [234 ]Cancer Registry of Norway, Oslo, Norway
                [235 ]Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
                [236 ]Department of Gynecology and Obstetrics, Helios Clinics Berlin-Buch, Berlin, Germany
                [237 ]Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
                [238 ]Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands
                [239 ]Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
                [240 ]Department of Gynaecology and Obstetrics, University of Ulm, Ulm, Germany
                [241 ]Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
                [242 ]Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
                [243 ]Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia
                [244 ]Seoul National University College of Medicine, Seoul, Korea
                [245 ]Armed Forces Capital Hospital, Seongnam, Korea
                [246 ]Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [247 ]Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
                [248 ]Department of Medicine, Institute for Human Genetics, UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
                [249 ]Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
                [250 ]QIMR Berghofer Medical Research Institute, Brisbane, Australia
                [251 ]Pathology Queensland, The Royal Brisbane and Women's Hospital, Brisbane 4029, Australia
                [252 ]Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
                [253 ]Center for Genomic Medicine, Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
                [254 ]University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [255 ]Department of Oncology, Södersjukhuset, Stockholm, Sweden
                [256 ]Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands
                Author notes
                [257]

                These authors jointly supervised this work.

                Correspondence should be addressed to D.F.E. ( dfe20@ 123456medschl.cam.ac.uk )
                Article
                Manuscript ID: EMS74191
                DOI: 10.1038/nature24284
                PMC ID: 5798588
                PubMed ID: 29059683
                SO-VID: f68419f3-a3af-4e41-a574-f3c7bcdbb980
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