Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

Details

Title
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Author
Law, Philip J 1   VIAFID ORCID Logo  ; Timofeeva, Maria 2   VIAFID ORCID Logo  ; Fernandez-Rozadilla Ceres 3   VIAFID ORCID Logo  ; Broderick, Peter 1   VIAFID ORCID Logo  ; Studd, James 1   VIAFID ORCID Logo  ; Fernandez-Tajes, Juan 4 ; Farrington, Susan 2   VIAFID ORCID Logo  ; Svinti Victoria 2   VIAFID ORCID Logo  ; Palles Claire 5 ; Orlando, Giulia 1 ; Sud Amit 1   VIAFID ORCID Logo  ; Holroyd, Amy 1 ; Penegar Steven 1 ; Theodoratou Evropi 6 ; Vaughan-Shaw, Peter 2 ; Campbell, Harry 6 ; Zgaga Lina 7 ; Hayward, Caroline 8   VIAFID ORCID Logo  ; Campbell, Archie 9   VIAFID ORCID Logo  ; Harris, Sarah 10 ; Deary, Ian J 11 ; Starr, John 12 ; Gatcombe Laura 13 ; Pinna, Maria 13 ; Briggs, Sarah 13 ; Martin, Lynn 13   VIAFID ORCID Logo  ; Jaeger, Emma 13 ; Sharma-Oates, Archana 13 ; East, James 14   VIAFID ORCID Logo  ; Leedham, Simon 15 ; Arnold, Roland 16 ; Johnstone, Elaine 17 ; Wang, Haitao 17 ; Kerr, David 18 ; Kerr, Rachel 17 ; Maughan, Tim 17 ; Kaplan, Richard 19   VIAFID ORCID Logo  ; Al-Tassan, Nada 20   VIAFID ORCID Logo  ; Palin Kimmo 21   VIAFID ORCID Logo  ; Hänninen, Ulrika A 21 ; Cajuso Tatiana 21 ; Tanskanen Tomas 21 ; Kondelin Johanna 21 ; Kaasinen Eevi 21 ; Sarin Antti-Pekka 22 ; Eriksson, Johan G 23 ; Rissanen Harri 24 ; Knekt, Paul 24 ; Pukkala Eero 25 ; Jousilahti Pekka 24 ; Salomaa Veikko 24   VIAFID ORCID Logo  ; Ripatti Samuli 26 ; Palotie Aarno 27 ; Renkonen-Sinisalo Laura 28 ; Lepistö, Anna 28 ; Böhm, Jan 29 ; Jukka-Pekka, Mecklin 30 ; Buchanan, Daniel D 31   VIAFID ORCID Logo  ; Aung-Ko, Win 32   VIAFID ORCID Logo  ; Hopper, John 32 ; Jenkins, Mark E 32   VIAFID ORCID Logo  ; Lindor Noralane M 33 ; Newcomb, Polly A 34 ; Gallinger, Steven 35 ; Duggan, David 36 ; Casey, Graham 37 ; Hoffmann, Per 38 ; Nöthen, Markus M 39 ; Jöckel Karl-Heinz 40 ; Easton, Douglas F 41   VIAFID ORCID Logo  ; Pharoah Paul D P 41   VIAFID ORCID Logo  ; Peto Julian 42 ; Canzian Federico 43 ; Swerdlow, Anthony 44 ; Eeles, Rosalind A 45   VIAFID ORCID Logo  ; Kote-Jarai Zsofia 1 ; Muir, Kenneth 46   VIAFID ORCID Logo  ; Pashayan Nora 47   VIAFID ORCID Logo  ; Henderson, Brian E 48 ; Haiman, Christopher A 48 ; Schumacher, Fredrick R 49 ; Al Olama Ali Amin 50 ; Benlloch Sara 51 ; Berndt, Sonja I 52 ; Conti, David V 48 ; Wiklund Fredrik 53 ; Chanock, Stephen 48 ; Gapstur, Susan 54 ; Stevens, Victoria L 54 ; Tangen, Catherine M 55 ; Batra Jyotsna 56 ; Clements, Judith 56 ; Gronberg Henrik 53 ; Schleutker Johanna 57 ; Albanes Demetrius 52 ; Wolk Alicja 58 ; West, Catharine 59 ; Mucci Lorelei 60 ; Cancel-Tassin Géraldine 61 ; Koutros Stella 52 ; Sorensen, Karina Dalsgaard 62 ; Grindedal, Eli Marie 63 ; Neal, David E 64 ; Hamdy, Freddie C 65 ; Donovan, Jenny L 66 ; Travis, Ruth C 67 ; Hamilton, Robert J 68 ; Ingles, Sue Ann 48 ; Rosenstein, Barry S 69 ; Yong-Jie, Lu 70 ; Giles, Graham G 71 ; Kibel, Adam S 72 ; Vega, Ana 73 ; Kogevinas Manolis 74 ; Penney, Kathryn L 75 ; Park, Jong Y 76 ; Stanford, Janet L 77 ; Cybulski Cezary 78 ; Nordestgaard, Børge G 79 ; Maier Christiane 80 ; Kim, Jeri 81 ; John, Esther M 82 ; Teixeira, Manuel R 83 ; Neuhausen, Susan L 84 ; Kim, De Ruyck 85 ; Razack Azad 86 ; Newcomb, Lisa F 87 ; Gamulin Marija 88 ; Kaneva Radka 89 ; Usmani Nawaid 90 ; Claessens, Frank 91 ; Townsend, Paul A 92 ; Gago-Dominguez, Manuela 93 ; Roobol, Monique J 94 ; Menegaux Florence 95 ; Kay-Tee, Khaw 96 ; Cannon-Albright, Lisa 97 ; Pandha Hardev 98 ; Thibodeau, Stephen N 99 ; Harkin, Andrea 100   VIAFID ORCID Logo  ; Allan, Karen 100 ; McQueen, John 100 ; James, Paul 100   VIAFID ORCID Logo  ; Iveson, Timothy 101 ; Saunders, Mark 102 ; Butterbach Katja 103 ; Chang-Claude, Jenny 104 ; Hoffmeister, Michael 103 ; Brenner, Hermann 105 ; Kirac Iva 106 ; Matošević Petar 107 ; Hofer Philipp 108   VIAFID ORCID Logo  ; Brezina, Stefanie 108   VIAFID ORCID Logo  ; Gsur Andrea 108 ; Cheadle, Jeremy P 109   VIAFID ORCID Logo  ; Aaltonen, Lauri A 21 ; Tomlinson, Ian 13   VIAFID ORCID Logo  ; Houlston Richard S 1   VIAFID ORCID Logo  ; Dunlop, Malcolm G 2 

1  The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623) 
2  University of Edinburgh, Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
3  Instituto de Investigación de Santiago, Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain (GRID:grid.4305.2); University of Birmingham, Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, Birmingham, UK (GRID:grid.6572.6) (ISNI:0000 0004 1936 7486) 
4  McCarthy Group, Wellcome Centre for Human Genetics, Oxford, UK (GRID:grid.18886.3f) 
5  University of Birmingham, Gastrointestinal Cancer Genetics Laboratory, Institute of Cancer and Genomic Sciences, Edgbaston, UK (GRID:grid.6572.6) (ISNI:0000 0004 1936 7486) 
6  University of Edinburgh, Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Centre for Global Health Research, Usher Institute, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
7  University of Edinburgh, Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Dublin, Department of Public Health and Primary Care, Institute of Population Health, Trinity College Dublin, Dublin, Ireland (GRID:grid.8217.c) (ISNI:0000 0004 1936 9705) 
8  University of Edinburgh, Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
9  University of Edinburgh, Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
10  University of Edinburgh, Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Department of Psychology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
11  University of Edinburgh, Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
12  University of Edinburgh, Generation Scotland, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988); University of Edinburgh, Alzheimer Scotland Dementia Research Centre, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
13  University of Birmingham, Cancer Genetics and Evolution Laboratory, Institute of Cancer and Genomic Sciences, Birmingham, UK (GRID:grid.6572.6) (ISNI:0000 0004 1936 7486) 
14  University of Oxford, John Radcliffe Hospital, Translational Gastroenterology Unit, Nuffield Department. of Medicine, Oxford, UK (GRID:grid.6572.6) 
15  McCarthy Group, Wellcome Centre for Human Genetics, Oxford, UK (GRID:grid.6572.6); University of Edinburgh, Alzheimer Scotland Dementia Research Centre, Edinburgh, UK (GRID:grid.4305.2) (ISNI:0000 0004 1936 7988) 
16  University of Birmingham, Cancer Bioinfomatics Laboratory, Institute of Cancer and Genomic Sciences, Birmingham, UK (GRID:grid.6572.6) (ISNI:0000 0004 1936 7486) 
17  University of Oxford, Department of Oncology, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
18  University of Oxford, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
19  Medical Research Council Clinical Trials Unit, London, UK (GRID:grid.415052.7) (ISNI:0000 0004 0606 323X) 
20  King Faisal Specialist Hospital and Research Center, Department of Genetics, Riyadh, Saudi Arabia (GRID:grid.415310.2) (ISNI:0000 0001 2191 4301) 
21  University of Helsinki, Department of Medical and Clinical Genetics, Medicum and Genome-Scale Biology Research Program, Research Programs Unit, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
22  University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
23  Folkhälsan Research Centre, Helsinki, Finland (GRID:grid.428673.c) (ISNI:0000 0004 0409 6302); University of Helsinki and Helsinki University Hospital, Unit of General Practice and Primary Health Care, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
24  National Institute for Health and Welfare, Helsinki, Finland (GRID:grid.14758.3f) (ISNI:0000 0001 1013 0499) 
25  University of Tampere, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland, and Faculty of Social Sciences, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254); University of Tampere, Faculty of Social Sciences, Tampere, Finland (GRID:grid.502801.e) (ISNI:0000 0001 2314 6254) 
26  University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); University of Helsinki, Department of Public Health, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) 
27  University of Helsinki, Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); Massachusetts General Hospital, Analytic and Translational Genetics Unit, Department of Medicine, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
28  Helsinki University Hospital, Department of Surgery, Abdominal Center, Helsinki, Finland (GRID:grid.15485.3d) (ISNI:0000 0000 9950 5666) 
29  Central Finland Central Hospital, Department of Pathology, Jyväskylä, Finland (GRID:grid.460356.2) (ISNI:0000 0004 0449 0385) 
30  Jyväskylä Central Hospital, Department of Surgery, Jyväskylä, Finland (GRID:grid.460356.2) (ISNI:0000 0004 0449 0385); University of Jyväskylä, Department of Health Sciences, Faculty of Sport and Health Sciences, Jyväskylä, Finland (GRID:grid.9681.6) (ISNI:0000 0001 1013 7965) 
31  The University of Melbourne, Colorectal Oncogenomics Group, Department of Clinical Pathology, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); University of Melbourne, Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Royal Melbourne Hospital, Genomic Medicine and Family Cancer Clinic, Parkville, Australia (GRID:grid.416153.4) (ISNI:0000 0004 0624 1200) 
32  The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
33  Mayo Clinic, Department of Health Sciences Research, Scottsdale, USA (GRID:grid.417468.8) (ISNI:0000 0000 8875 6339) 
34  Fred Hutchinson Cancer Research Center, Cancer Prevention Program, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
35  Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada (GRID:grid.250674.2) (ISNI:0000 0004 0626 6184) 
36  Translational Genomics Research Institute (TGen), An Affiliate of City of Hope, Phoenix, USA (GRID:grid.250942.8) (ISNI:0000 0004 0507 3225) 
37  University of Virginia, Center for Public Health Genomics, Virginia, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
38  University of Basel, Human Genomics Research Group, Department of Biomedicine, Basel, Switzerland (GRID:grid.6612.3) (ISNI:0000 0004 1937 0642); University of Bonn, Department of Genomics, Life & Brain Center, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
39  University of Bonn, Department of Genomics, Life & Brain Center, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300); University of Bonn School of Medicine & University Hospital Bonn, Institute of Human Genetics, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300) 
40  University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany (GRID:grid.5718.b) (ISNI:0000 0001 2187 5445) 
41  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
42  London School of Hygiene and Tropical Medicine, Department of Non-Communicable Disease Epidemiology, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
43  German Cancer Research Center (DKFZ), Genomic Epidemiology Group, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
44  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) 
45  The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623); Royal Marsden NHS Foundation Trust, London, UK (GRID:grid.5072.0) (ISNI:0000 0001 0304 893X) 
46  University of Manchester, Division of Population Health, Health Services Research and Primary Care, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407); University of Warwick, Warwick Medical School, Coventry, UK (GRID:grid.7372.1) (ISNI:0000 0000 8809 1613) 
47  University College London, Department of Applied Health Research, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201); University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
48  University of Southern California/Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
49  Case Western Reserve University, Department of Epidemiology and Biostatistics, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); University Hospitals, Seidman Cancer Center, Cleveland, USA (GRID:grid.241104.2) (ISNI:0000 0004 0452 4020) 
50  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Department of Clinical Neurosciences, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
51  The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK (GRID:grid.18886.3f) (ISNI:0000 0001 1271 4623); University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
52  NIH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
53  Karolinska Institute, Department of Medical Epidemiology and Biostatistics, Stockholm, Sweden (GRID:grid.4714.6) (ISNI:0000 0004 1937 0626) 
54  American Cancer Society, Epidemiology Research Program, Atlanta, USA (GRID:grid.422418.9) (ISNI:0000 0004 0371 6485) 
55  Fred Hutchinson Cancer Research Center, SWOG Statistical Center, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622) 
56  Queensland University of Technology, Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953); Translational Research Institute, Brisbane, Australia (GRID:grid.489335.0) (ISNI:0000000406180938) 
57  University of Turku, Department of Medical Biochemistry and Genetics, Institute of Biomedicine, Turku, Finland (GRID:grid.1374.1) (ISNI:0000 0001 2097 1371); Turku University Hospital, Tyks Microbiology and Genetics, Department of Medical Genetics, Turku, Finland (GRID:grid.410552.7) (ISNI:0000 0004 0628 215X) 
58  Karolinska Institutet, Division of Nutritional Epidemiology, 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) 
59  The Christie Hospital NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, Manchester NIHR Biomedical Research Centre, Manchester, UK (GRID:grid.412917.8) (ISNI:0000 0004 0430 9259) 
60  Harvard T.H Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
61  Tenon Hospital, CeRePP, Paris, France (GRID:grid.413483.9) (ISNI:0000 0001 2259 4338); Tenon Hospital, Sorbonne Université, GRC n°5 ONCOTYPE-URO, Paris, France (GRID:grid.413483.9) (ISNI:0000 0001 2259 4338) 
62  Aarhus University Hospital, Department of Molecular Medicine, Aarhus, Denmark (GRID:grid.154185.c) (ISNI:0000 0004 0512 597X); Aarhus University, Department of Clinical Medicine, Aarhus, Denmark (GRID:grid.7048.b) (ISNI:0000 0001 1956 2722) 
63  Oslo University Hospital, Department of Medical Genetics, Oslo, Norway (GRID:grid.55325.34) (ISNI:0000 0004 0389 8485) 
64  University of Cambridge, Department of Oncology, Addenbrooke’s Hospital, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Oxford, Nuffield Department of Surgical Sciences, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, Faculty of Medical Science, John Radcliffe Hospital, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
65  University of Oxford, Nuffield Department of Surgical Sciences, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948); University of Oxford, Faculty of Medical Science, John Radcliffe Hospital, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
66  University of Bristol, School of Social and Community Medicine, Bristol, UK (GRID:grid.5337.2) (ISNI:0000 0004 1936 7603) 
67  Nuffield Department of Population Health University of Oxford, Cancer Epidemiology Unit, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
68  Princess Margaret Cancer Centre, Department of Surgical Oncology, Toronto, Canada (GRID:grid.415224.4) (ISNI:0000 0001 2150 066X) 
69  Icahn School of Medicine at Mount Sinai, Department of Radiation Oncology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
70  Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133) 
71  The Cancer Council Victoria, Cancer Epidemiology & Intelligence 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) 
72  Brigham and Womens Hospital, Division of Urologic Surgery, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
73  IDIS, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, Santiago de Compostela, Spain (GRID:grid.488911.d) (ISNI:0000 0004 0408 4897) 
74  Barcelona Institute for Global Health (ISGlobal), Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain (GRID:grid.434607.2) (ISNI:0000 0004 1763 3517); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); IMIM (Hospital del Mar Research Institute), Barcelona, Spain (GRID:grid.411142.3) (ISNI:0000 0004 1767 8811); Universitat Pompeu Fabra, Barcelona, Spain (GRID:grid.5612.0) (ISNI:0000 0001 2172 2676) 
75  Brigham and Women’s Hospital/Harvard Medical School, Channing Division of Network Medicine, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294) 
76  Moffitt Cancer Center, Department of Cancer Epidemiology, Tampa, USA (GRID:grid.468198.a) (ISNI:0000 0000 9891 5233) 
77  Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Epidemiology, School of Public Health, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
78  Pomeranian Medical University, International Hereditary Cancer Center, Department of Genetics and Pathology, Szczecin, Poland (GRID:grid.107950.a) (ISNI:0000 0001 1411 4349) 
79  University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark (GRID:grid.5254.6) (ISNI:0000 0001 0674 042X); Copenhagen University Hospital, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Herlev, Denmark (GRID:grid.4973.9) (ISNI:0000 0004 0646 7373) 
80  University Hospital Ulm, Institute for Human Genetics, Ulm, Germany (GRID:grid.410712.1) 
81  The University of Texas MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
82  Cancer Prevention Institute of California, Fremont, USA (GRID:grid.280669.3) (ISNI:0000 0004 0498 8300); Stanford University School of Medicine, Department of Health Research & Policy (Epidemiology) and Stanford Cancer Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
83  Portuguese Oncology Institute of Porto, 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) 
84  Beckman Research Institute of the City of Hope, Department of Population Sciences, Duarte, USA (GRID:grid.410425.6) (ISNI:0000 0004 0421 8357) 
85  Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium (GRID:grid.5342.0) (ISNI:0000 0001 2069 7798) 
86  University of Malaya, Faculty of Medicine, Department of Surgery, Kuala Lumpur, Malaysia (GRID:grid.10347.31) (ISNI:0000 0001 2308 5949) 
87  Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, USA (GRID:grid.270240.3) (ISNI:0000 0001 2180 1622); University of Washington, Department of Urology, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
88  University Hospital Centre Zagreb, Division of Medical Oncology, Urogenital Unit, Department of Oncology, Zagreb, Croatia (GRID:grid.412688.1) (ISNI:0000 0004 0397 9648) 
89  Medical University, Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Sofia, Bulgaria (GRID:grid.410563.5) (ISNI:0000 0004 0621 0092) 
90  University of Alberta, Department of Oncology, Cross Cancer Institute, Edmonton, Canada (GRID:grid.17089.37); Cross Cancer Institute, Division of Radiation Oncology, Edmonton, Canada (GRID:grid.17089.37) 
91  Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Belgium (GRID:grid.17089.37) 
92  St Mary’s Hospital, Institute of Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK (GRID:grid.416523.7) (ISNI:0000 0004 0641 2620) 
93  Instituto de Investigación de Santiago, Grupo de Medicina Xenómica, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain (GRID:grid.416523.7); Moores Cancer Center, University of California San Diego, La Jolla, USA (GRID:grid.416523.7) 
94  Erasmus University Medical Center, Department of Urology, Rotterdam, the Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
95  University Paris-Saclay, Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, Villejuif, France (GRID:grid.460789.4) (ISNI:0000 0004 4910 6535) 
96  University of Cambridge, Clinical Gerontology Unit, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
97  University of Utah School of Medicine, Division of Genetic Epidemiology, Department of Medicine, Salt Lake City, USA (GRID:grid.223827.e) (ISNI:0000 0001 2193 0096); George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, USA (GRID:grid.413886.0) 
98  The University of Surrey, Guildford, UK (GRID:grid.5475.3) (ISNI:0000 0004 0407 4824) 
99  Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
100  University of Glasgow, Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, Glasgow, UK (GRID:grid.8756.c) (ISNI:0000 0001 2193 314X) 
101  University Hospital Southampton NHS Foundation Trust, Southampton, UK (GRID:grid.430506.4) 
102  The Christie NHS Foundation Trust, Manchester, UK (GRID:grid.412917.8) (ISNI:0000 0004 0430 9259) 
103  Deutsches Krebsforschungszentrum, Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584) 
104  German Cancer Research Center (DKFZ), Unit of Genetic Epidemiology, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484) 
105  Deutsches Krebsforschungszentrum, Division of Clinical Epidemiology and Aging Research, Heidelberg, Germany (GRID:grid.7497.d) (ISNI:0000 0004 0492 0584); German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 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) 
106  Sestre milosrdnice University Hospital Centre, Department of Surgical Oncology, University Hospital for Tumours, Zagreb, Croatia (GRID:grid.412488.3) (ISNI:0000 0000 9336 4196) 
107  University Hospital Center Zagreb, Department of Surgery, Zagreb, Croatia (GRID:grid.412688.1) (ISNI:0000 0004 0397 9648) 
108  Medical University of Vienna, Department of Medicine I, Institute of Cancer Research, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492) 
109  Cardiff University, Division of Cancer and Genetics, School of Medicine, Cardiff, UK (GRID:grid.5600.3) (ISNI:0000 0001 0807 5670) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-09775-w
ProQuest document ID
2225123492
Copyright
© The Author(s) 2019. 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.