Abstract

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Details

Title
A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
Author
Escala-Garcia, Maria 1 ; Abraham, Jean 2 ; Andrulis, Irene L 3   VIAFID ORCID Logo  ; Anton-Culver, Hoda 4 ; Arndt, Volker 5   VIAFID ORCID Logo  ; Ashworth, Alan 6 ; Auer, Paul L 7 ; Auvinen Päivi 8 ; Beckmann, Matthias W 9 ; Beesley, Jonathan 10 ; Behrens, Sabine 11 ; Benitez, Javier 12 ; Bermisheva Marina 13 ; Blomqvist, Carl 14 ; Blot, William 15 ; Bogdanova, Natalia V 16 ; Bojesen, Stig E 17   VIAFID ORCID Logo  ; Bolla, Manjeet K 18 ; Børresen-Dale Anne-Lise 19 ; Brauch Hiltrud 20   VIAFID ORCID Logo  ; Brenner, Hermann 21 ; Brucker, Sara Y 22 ; Burwinkel, Barbara 23 ; Caldas, Carlos 24   VIAFID ORCID Logo  ; Canzian Federico 25   VIAFID ORCID Logo  ; Chang-Claude, Jenny 26 ; Chanock, Stephen J 27   VIAFID ORCID Logo  ; Chin Suet-Feung 28   VIAFID ORCID Logo  ; Clarke, Christine L 29 ; Couch, Fergus J 30 ; Cox, Angela 31 ; Cross, Simon S 32 ; Czene Kamila 33 ; Daly, Mary B 34 ; Dennis, Joe 18   VIAFID ORCID Logo  ; Devilee, Peter 35   VIAFID ORCID Logo  ; Dunn, Janet A 36 ; Dunning, Alison M 37   VIAFID ORCID Logo  ; Dwek, Miriam 38   VIAFID ORCID Logo  ; Earl, Helena M 39 ; Eccles, Diana M 40 ; Heather, Eliassen A 41 ; Ellberg Carolina 42   VIAFID ORCID Logo  ; Gareth, Evans D 43 ; Fasching, Peter A 44   VIAFID ORCID Logo  ; Figueroa Jonine 45 ; Flyger Henrik 46 ; Gago-Dominguez, Manuela 47 ; Gapstur, Susan M 48 ; García-Closas Montserrat 49   VIAFID ORCID Logo  ; García-Sáenz, José A 50   VIAFID ORCID Logo  ; Gaudet, Mia M 48 ; George, Angela 51 ; Giles, Graham G 52   VIAFID ORCID Logo  ; Goldgar, David E 53 ; González-Neira, Anna 54 ; Grip Mervi 55 ; Guénel Pascal 56   VIAFID ORCID Logo  ; Guo, Qi 57 ; Haiman, Christopher A 58 ; Håkansson Niclas 59   VIAFID ORCID Logo  ; Hamann Ute 60 ; Harrington, Patricia A 37 ; Hiller, Louise 36 ; Hooning Maartje J 61 ; Hopper, John L 62 ; Howell, Anthony 63 ; Huang Chiun-Sheng 64 ; Huang Guanmengqian 60 ; Hunter, David J 65 ; Jakubowska, Anna 66 ; John, Esther M 67 ; Kaaks Rudolf 11 ; Kapoor, Pooja Middha 68   VIAFID ORCID Logo  ; Keeman Renske 1   VIAFID ORCID Logo  ; Kitahara, Cari M 69 ; Koppert, Linetta B 70 ; Kraft, Peter 71   VIAFID ORCID Logo  ; Kristensen, Vessela N 19 ; Lambrechts Diether 72   VIAFID ORCID Logo  ; Le Marchand Loic 73 ; Lejbkowicz Flavio 74 ; Lindblom Annika 75 ; Lubiński Jan 76 ; Mannermaa Arto 77 ; Manoochehri Mehdi 60 ; Manoukian Siranoush 78 ; Margolin, Sara 79 ; Martinez, Maria Elena 80 ; Maurer Tabea 81 ; Mavroudis Dimitrios 82 ; Meindl Alfons 83 ; Milne, Roger L 84   VIAFID ORCID Logo  ; Mulligan, Anna Marie 85 ; Neuhausen, Susan L 86 ; Nevanlinna Heli 87   VIAFID ORCID Logo  ; Newman, William G 88   VIAFID ORCID Logo  ; Olshan, Andrew F 89 ; Olson, Janet E 90   VIAFID ORCID Logo  ; Olsson Håkan 42 ; Orr, Nick 91   VIAFID ORCID Logo  ; Peterlongo Paolo 92   VIAFID ORCID Logo  ; Petridis Christos 93 ; Prentice, Ross L 94 ; Presneau Nadege 38 ; Punie Kevin 95   VIAFID ORCID Logo  ; Ramachandran Dhanya 96   VIAFID ORCID Logo  ; Rennert Gad 97   VIAFID ORCID Logo  ; Romero Atocha 98   VIAFID ORCID Logo  ; Sachchithananthan Mythily 29 ; Saloustros Emmanouil 99   VIAFID ORCID Logo  ; Sawyer, Elinor J 93 ; Schmutzler, Rita K 100 ; Schwentner Lukas 101 ; Scott, Christopher 90   VIAFID ORCID Logo  ; Simard, Jacques 102   VIAFID ORCID Logo  ; Sohn Christof 103 ; Southey, Melissa C 104 ; Swerdlow, Anthony J 105 ; Tamimi, Rulla M 106 ; Tapper, William J 107 ; Teixeira, Manuel R 108   VIAFID ORCID Logo  ; Terry, Mary Beth 109 ; Thorne, Heather 110 ; Tollenaar Rob A E M 111 ; Tomlinson, Ian 112   VIAFID ORCID Logo  ; Troester, Melissa A 89 ; Truong Thérèse 56   VIAFID ORCID Logo  ; Turnbull, Clare 51 ; Vachon, Celine M 90 ; van der Kolk Lizet E 113 ; Wang, Qin 18 ; Winqvist, Robert 114   VIAFID ORCID Logo  ; Wolk Alicja 115   VIAFID ORCID Logo  ; Yang, Xiaohong R 27 ; Ziogas Argyrios 4   VIAFID ORCID Logo  ; Pharoah Paul D P 116   VIAFID ORCID Logo  ; Hall, Per 117 ; Wessels Lodewyk F A 118 ; Chenevix-Trench Georgia 10 ; Bader, Gary D 119   VIAFID ORCID Logo  ; Dörk Thilo 96   VIAFID ORCID Logo  ; Easton, Douglas F 116   VIAFID ORCID Logo  ; Sander, Canisius 120   VIAFID ORCID Logo  ; Schmidt, Marjanka K 121   VIAFID ORCID Logo 

 The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, The Netherlands (GRID:grid.430814.a) 
 University of Cambridge, Department of Oncology, Centre for Cancer Genetic Epidemiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cambridge Experimental Cancer Medicine Centre, Cambridge, UK (GRID:grid.5335.0); University of Cambridge NHS Foundation Hospitals, Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, Canada (GRID:grid.250674.2) (ISNI:0000 0004 0626 6184); University of Toronto, Department of Molecular Genetics, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
 University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, USA (GRID:grid.266093.8) (ISNI:0000 0001 0668 7243) 
 German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
 University of California San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
 Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Wisconsin-Milwaukee, Zilber School of Public Health, Milwaukee, USA (GRID:grid.267468.9) (ISNI:0000 0001 0695 7223) 
 Kuopio University Hospital, Cancer Center, Kuopio, Finland (GRID:grid.410705.7) (ISNI:0000 0004 0628 207X); University of Eastern Finland, Institute of Clinical Medicine, Oncology, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490); University of Eastern Finland, Translational Cancer Research Area, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490) 
 University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany (GRID:grid.9668.1) 
10  QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
11  German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
12  Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain (GRID:grid.7719.8) (ISNI:0000 0000 8700 1153); Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain (GRID:grid.452372.5) (ISNI:0000 0004 1791 1185) 
13  Ufa Scientific Center of Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia (GRID:grid.452372.5) 
14  Helsinki University Hospital, University of Helsinki, Department of Oncology, Helsinki, Finland (GRID:grid.452372.5); Örebro University Hospital, Department of Oncology, Örebro, Sweden (GRID:grid.412367.5) (ISNI:0000 0001 0123 6208) 
15  Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217); International Epidemiology Institute, Rockville, USA (GRID:grid.419344.f) (ISNI:0000 0004 0384 6204) 
16  Hannover Medical School, Department of Radiation Oncology, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877); Hannover Medical School, Gynaecology Research Unit, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877); N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (GRID:grid.10423.34) 
17  Copenhagen University Hospital, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373); University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X) 
18  University of Cambridge, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
19  Oslo University Hospital-Radiumhospitalet, Department of Cancer Genetics, Institute for Cancer Research, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485); University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway (GRID:grid.5510.1) (ISNI:0000 0004 1936 8921) 
20  Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (GRID:grid.502798.1) (ISNI:0000 0004 0561 903X); University of Tuebingen, iFIT-Cluster of Excellence, Tuebingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
21  German Cancer Research Center (DKFZ), Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Division of Preventive Oncology, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
22  University of Tübingen, Department of Gynecology and Obstetrics, Tübingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447) 
23  German Cancer Research Center (DKFZ), Molecular Epidemiology Group, C080, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); University of Heidelberg, Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
24  University of Cambridge, Cancer Research UK Cambridge Institute, Department of Oncology, Li Ka Shing Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Cambridge University Hospitals NHS Foundation Trust, Breast Cancer Programme, CRUK Cambridge Cancer Centre and NIHR Biomedical Research Centre, Cambridge, UK (GRID:grid.24029.3d) (ISNI:0000 0004 0383 8386) 
25  German Cancer Research Center (DKFZ), Genomic Epidemiology Group, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
26  German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); University Medical Center Hamburg-Eppendorf, Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484) 
27  National Cancer Institute, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
28  University of Cambridge, Cancer Research UK Cambridge Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
29  University of Sydney, Westmead Institute for Medical Research, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
30  Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
31  University of Sheffield, Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), Sheffield, UK (GRID:grid.11835.3e) (ISNI:0000 0004 1936 9262) 
32  University of Sheffield, Academic Unit of Pathology, Department of Neuroscience, Sheffield, UK (GRID:grid.11835.3e) (ISNI:0000 0004 1936 9262) 
33  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
34  Fox Chase Cancer Center, Department of Clinical Genetics, Philadelphia, USA (GRID:grid.412530.1) (ISNI:0000 0004 0456 6466) 
35  Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978); Leiden University Medical Center, Department of Human Genetics, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
36  University of Warwick, Warwick Clinical Trials Unit, Coventry, UK (GRID:grid.7372.1) (ISNI:0000 0000 8809 1613) 
37  University of Cambridge, Department of Oncology, Centre for Cancer Genetic Epidemiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
38  University of Westminster, Department of Biomedical Sciences, Faculty of Science and Technology, London, UK (GRID:grid.12896.34) (ISNI:0000 0000 9046 8598) 
39  University of Cambridge NHS Foundation Hospitals, Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
40  University of Southampton, Cancer Sciences Academic Unit, Faculty of Medicine, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
41  Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
42  Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund, Sweden (GRID:grid.4514.4) (ISNI:0000 0001 0930 2361) 
43  University of Manchester, Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Genomic Medicine, St Mary’s Hospital, Manchester Centre for Genomic Medicine, Manchester, UK (GRID:grid.462482.e) (ISNI:0000 0004 0417 0074); Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK (GRID:grid.498924.a) 
44  University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany (GRID:grid.498924.a); University of California at Los Angeles, Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718) 
45  National Cancer Institute, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); The University of Edinburgh Medical School, Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); Cancer Research UK Edinburgh Centre, Edinburgh, UK (GRID:grid.4305.2) 
46  Copenhagen University Hospital, Department of Breast Surgery, Herlev and Gentofte Hospital, Herlev, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373) 
47  Complejo Hospitalario Universitario de Santiago, SERGAS, Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain (GRID:grid.411048.8) (ISNI:0000 0000 8816 6945); University of California San Diego, Moores Cancer Center, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
48  American Cancer Society, Epidemiology Research Program, Atlanta, USA (GRID:grid.422418.9) (ISNI:0000 0004 0371 6485) 
49  National Cancer Institute, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075); Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
50  Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427) 
51  The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
52  Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, Australia (GRID:grid.3263.4) (ISNI:0000 0001 1482 3639); The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
53  University of Utah School of Medicine, Department of Dermatology, Huntsman Cancer Institute, Salt Lake City, USA (GRID:grid.223827.e) (ISNI:0000 0001 2193 0096) 
54  Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain (GRID:grid.7719.8) (ISNI:0000 0000 8700 1153) 
55  University of Oulu, Department of Surgery, Oulu University Hospital, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873) 
56  University Paris-Saclay, INSERM, University Paris-Sud, Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), Villejuif, France (GRID:grid.5842.b) (ISNI:0000 0001 2171 2558) 
57  University of Cambridge, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
58  University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
59  Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
60  German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
61  Erasmus MC Cancer Institute, Department of Medical Oncology, Family Cancer Clinic, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
62  The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
63  University of Manchester, Division of Cancer Sciences, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407) 
64  National Taiwan University Hospital and National Taiwan University College of Medicine, Department of Surgery, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241) 
65  Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Program in Genetic Epidemiology and Statistical Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); University of Oxford, Nuffield Department of Population Health, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
66  Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland (GRID:grid.107950.a) (ISNI:0000 0001 1411 4349); Pomeranian Medical University, Independent Laboratory of Molecular Biology and Genetic Diagnostics, Szczecin, Poland (GRID:grid.107950.a) (ISNI:0000 0001 1411 4349) 
67  Stanford Cancer Institute, Stanford University School of Medicine, Division of Oncology, Department of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
68  German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); University of Heidelberg, Faculty of Medicine, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
69  National Cancer Institute, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Bethesda, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
70  Erasmus MC Cancer Institute, Department of Surgical Oncology, Family Cancer Clinic, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
71  Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Program in Genetic Epidemiology and Statistical Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
72  VIB, VIB Center for Cancer Biology, Leuven, Belgium (GRID:grid.11486.3a) (ISNI:0000000104788040); University of Leuven, Laboratory for Translational Genetics, Department of Human Genetics, Leuven, Belgium (GRID:grid.5596.f) (ISNI:0000 0001 0668 7884) 
73  University of Hawaii Cancer Center, Epidemiology Program, Honolulu, USA (GRID:grid.410445.0) (ISNI:0000 0001 2188 0957) 
74  Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel (GRID:grid.410445.0) 
75  Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Karolinska University Hospital, Department of Clinical Genetics, Stockholm, Sweden (GRID:grid.24381.3c) (ISNI:0000 0000 9241 5705) 
76  Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland (GRID:grid.107950.a) (ISNI:0000 0001 1411 4349) 
77  University of Eastern Finland, Translational Cancer Research Area, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490); University of Eastern Finland, Institute of Clinical Medicine, Pathology and Forensic Medicine, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490); Kuopio University Hospital, Department of Clinical Pathology, Imaging Center, Kuopio, Finland (GRID:grid.410705.7) (ISNI:0000 0004 0628 207X) 
78  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT), Unit of Medical Genetics, Department of Medical Oncology and Hematology, Milan, Italy (GRID:grid.417893.0) (ISNI:0000 0001 0807 2568) 
79  Sšdersjukhuset, Department of Oncology, Stockholm, Sweden (GRID:grid.417893.0); Karolinska Institutet, Department of Clinical Science and Education, Sšdersjukhuset, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
80  University of California San Diego, Moores Cancer Center, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); University of California San Diego, Department of Family Medicine and Public Health, La Jolla, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
81  University Medical Center Hamburg-Eppendorf, Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484) 
82  University Hospital of Heraklion, Department of Medical Oncology, Heraklion, Greece (GRID:grid.412481.a) 
83  Ludwig Maximilian University of Munich, Department of Gynecology and Obstetrics, Munich, Germany (GRID:grid.5252.0) (ISNI:0000 0004 1936 973X) 
84  Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, Australia (GRID:grid.3263.4) (ISNI:0000 0001 1482 3639); The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
85  University of Toronto, Department of Laboratory Medicine and Pathobiology, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University Health Network, Laboratory Medicine Program, Toronto, Canada (GRID:grid.231844.8) (ISNI:0000 0004 0474 0428) 
86  Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, USA (GRID:grid.410425.6) (ISNI:0000 0004 0421 8357) 
87  University of Helsinki, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
88  University of Manchester, Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Genomic Medicine, St Mary’s Hospital, Manchester Centre for Genomic Medicine, Manchester, UK (GRID:grid.462482.e) (ISNI:0000 0004 0417 0074) 
89  University of North Carolina at Chapel Hill, Department of Epidemiology, Lineberger Comprehensive Cancer Center, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000000122483208) 
90  Mayo Clinic, Department of Health Sciences Research, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
91  Queen’s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, UK (GRID:grid.4777.3) (ISNI:0000 0004 0374 7521) 
92  IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Genome Diagnostics Program, Milan, Italy (GRID:grid.4777.3) 
93  King’s College London, Research Oncology, Guy’s Hospital, London, UK (GRID:grid.13097.3c) (ISNI:0000 0001 2322 6764) 
94  Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
95  Leuven Cancer Institute, University Hospitals Leuven, Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven, Belgium (GRID:grid.410569.f) (ISNI:0000 0004 0626 3338) 
96  Hannover Medical School, Gynaecology Research Unit, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877) 
97  Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel (GRID:grid.10423.34) 
98  Hospital Universitario Puerta de Hierro, Medical Oncology Department, Madrid, Spain (GRID:grid.73221.35) (ISNI:0000 0004 1767 8416) 
99  University Hospital of Larissa, Department of Oncology, Larissa, Greece (GRID:grid.411299.6) 
100  University Hospital of Cologne, Center for Hereditary Breast and Ovarian Cancer, Cologne, Germany (GRID:grid.411097.a) (ISNI:0000 0000 8852 305X); University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777) 
101  University Hospital Ulm, Department of Gynaecology and Obstetrics, Ulm, Germany (GRID:grid.410712.1) 
102  Centre Hospitalier Universitaire de Québec - Université Laval, Genomics Center, Research Center, Québec City, Canada (GRID:grid.23856.3a) (ISNI:0000 0004 1936 8390) 
103  University of Heidelberg, National Center for Tumor Diseases, Heidelberg, Germany (GRID:grid.7700.0) (ISNI:0000 0001 2190 4373) 
104  Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); The University of Melbourne, Department of Clinical Pathology, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
105  The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623); The Institute of Cancer Research, Division of Breast Cancer Research, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
106  Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard T.H. Chan School of Public Health, Program in Genetic Epidemiology and Statistical Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
107  University of Southampton, Faculty of Medicine, Southampton, UK (GRID:grid.5491.9) (ISNI:0000 0004 1936 9297) 
108  Portuguese Oncology Institute, Department of Genetics, Porto, Portugal (GRID:grid.418711.a) (ISNI:0000 0004 0631 0608); University of Porto, Biomedical Sciences Institute (ICBAS), Porto, Portugal (GRID:grid.5808.5) (ISNI:0000 0001 1503 7226) 
109  Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, USA (GRID:grid.21729.3f) (ISNI:0000000419368729) 
110  Peter MacCallum Cancer Center, Melbourne, Australia (GRID:grid.1055.1) (ISNI:0000000403978434); The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
111  Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands (GRID:grid.10419.3d) (ISNI:0000000089452978) 
112  University of Birmingham, Institute of Cancer and Genomic Sciences, Birmingham, UK (GRID:grid.6572.6) (ISNI:0000 0004 1936 7486); University of Oxford, Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
113  The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Family Cancer Clinic, Amsterdam, The Netherlands (GRID:grid.430814.a) 
114  University of Oulu, Biocenter Oulu, Cancer and Translational Medicine Research Unit, Laboratory of Cancer Genetics and Tumor Biology, Oulu, Finland (GRID:grid.10858.34) (ISNI:0000 0001 0941 4873); Northern Finland Laboratory Centre Oulu, Laboratory of Cancer Genetics and Tumor Biology, Oulu, Finland (GRID:grid.10858.34) 
115  Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Uppsala University, Department of Surgical Sciences, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
116  University of Cambridge, Department of Oncology, Centre for Cancer Genetic Epidemiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
117  Karolinska Institutet, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626); Sšdersjukhuset, Department of Oncology, Stockholm, Sweden (GRID:grid.4714.6) 
118  The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Carcinogenesis, Amsterdam, The Netherlands (GRID:grid.430814.a); Delft University of Technology, Faculty of EEMCS, Delft, The Netherlands (GRID:grid.5292.c) (ISNI:0000 0001 2097 4740) 
119  University of Toronto, Department of Molecular Genetics, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, The Donnelly Centre, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
120  The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, The Netherlands (GRID:grid.430814.a); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Carcinogenesis, Amsterdam, The Netherlands (GRID:grid.430814.a) 
121  The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, The Netherlands (GRID:grid.430814.a); The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands (GRID:grid.430814.a) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2342509404
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.