Abstract

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Details

Title
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Author
Dadaev, Tokhir 1   VIAFID ORCID Logo  ; Saunders, Edward J 1 ; Newcombe, Paul J 2 ; Anokian, Ezequiel 1 ; Leongamornlert, Daniel A 3   VIAFID ORCID Logo  ; Brook, Mark N 1   VIAFID ORCID Logo  ; Cieza-Borrella, Clara 1 ; Mijuskovic, Martina 1 ; Wakerell, Sarah 1 ; Ali Amin Al Olama 4   VIAFID ORCID Logo  ; Schumacher, Fredrick R 5   VIAFID ORCID Logo  ; Berndt, Sonja I 6 ; Benlloch, Sara 7 ; Mahbubl Ahmed 1 ; Goh, Chee 1 ; Sheng, Xin 8 ; Zhang, Zhuo 8 ; Muir, Kenneth 9   VIAFID ORCID Logo  ; Koveela Govindasami 1 ; Lophatananon, Artitaya 9 ; Stevens, Victoria L 10 ; Gapstur, Susan M 10 ; Carter, Brian D 10 ; Tangen, Catherine M 11 ; Goodman, Phyllis 11 ; Thompson, Ian M, Jr 12 ; Batra, Jyotsna 13   VIAFID ORCID Logo  ; Chambers, Suzanne 14 ; Moya, Leire 13 ; Clements, Judith 13 ; Horvath, Lisa 15 ; Tilley, Wayne 16 ; Risbridger, Gail 17 ; Gronberg, Henrik 18 ; Aly, Markus 19 ; Nordström, Tobias 20   VIAFID ORCID Logo  ; Pharoah, Paul 21   VIAFID ORCID Logo  ; Pashayan, Nora 22   VIAFID ORCID Logo  ; Schleutker, Johanna 23   VIAFID ORCID Logo  ; Tammela, Teuvo L J 24 ; Sipeky, Csilla 25   VIAFID ORCID Logo  ; Auvinen, Anssi 26 ; Albanes, Demetrius 6 ; Weinstein, Stephanie 6 ; Wolk, Alicja 27   VIAFID ORCID Logo  ; Hakansson, Niclas 27 ; West, Catharine 28 ; Dunning, Alison M 29 ; Burnet, Neil 30 ; Mucci, Lorelei 31 ; Giovannucci, Edward 31 ; Andriole, Gerald 32 ; Cussenot, Olivier 33 ; Cancel-Tassin, Géraldine 33   VIAFID ORCID Logo  ; Koutros, Stella 6 ; Beane Freeman, Laura E 6 ; Karina Dalsgaard Sorensen 34   VIAFID ORCID Logo  ; Torben Falck Orntoft 34 ; Borre, Michael 35 ; Maehle, Lovise 36 ; Grindedal, Eli Marie 36 ; Neal, David E 37 ; Donovan, Jenny L 38 ; Hamdy, Freddie C 39 ; Martin, Richard M 40 ; Travis, Ruth C 41 ; Key, Tim J 41 ; Hamilton, Robert J 42 ; Fleshner, Neil E 42 ; Finelli, Antonio 42 ; Ingles, Sue Ann 8 ; Stern, Mariana C 8 ; Rosenstein, Barry 43 ; Kerns, Sarah 44   VIAFID ORCID Logo  ; Ostrer, Harry 45   VIAFID ORCID Logo  ; Yong-Jie, Lu 46 ; Hong-Wei, Zhang 47 ; Feng, Ninghan 48 ; Mao, Xueying 46 ; Guo, Xin 49 ; Wang, Guomin 50 ; Sun, Zan 51 ; Giles, Graham G 52 ; Southey, Melissa C 53 ; MacInnis, Robert J 52 ; FitzGerald, Liesel M 54 ; Kibel, Adam S 55 ; Drake, Bettina F 32 ; Vega, Ana 56 ; Gómez-Caamaño, Antonio 57 ; Fachal, Laura 58   VIAFID ORCID Logo  ; Szulkin, Robert 59 ; Eklund, Martin 18 ; Kogevinas, Manolis 60   VIAFID ORCID Logo  ; Llorca, Javier 61 ; Castaño-Vinyals, Gemma 60 ; Penney, Kathryn L 62 ; Stampfer, Meir 62 ; Park, Jong Y 63 ; Sellers, Thomas A 63 ; Hui-Yi, Lin 64 ; Stanford, Janet L 65 ; Cybulski, Cezary 66 ; Wokolorczyk, Dominika 66 ; Lubinski, Jan 66 ; Ostrander, Elaine A 67 ; Geybels, Milan S 68 ; Nordestgaard, Børge G 69   VIAFID ORCID Logo  ; Nielsen, Sune F 69 ; Weisher, Maren 70 ; Bisbjerg, Rasmus 71 ; Martin, Andreas Røder 72 ; Iversen, Peter 73 ; Brenner, Hermann 74 ; Cuk, Katarina 75 ; Holleczek, Bernd 76 ; Maier, Christiane 77 ; Luedeke, Manuel 77 ; Schnoeller, Thomas 78 ; Kim, Jeri 79 ; Logothetis, Christopher J 79 ; John, Esther M 80 ; Teixeira, Manuel R 81 ; Paulo, Paula 82 ; Cardoso, Marta 82 ; Neuhausen, Susan L 83 ; Steele, Linda 83 ; Ding, Yuan Chun 83 ; Kim De Ruyck 84 ; De Meerleer, Gert 84 ; Ost, Piet 85 ; Razack, Azad 86 ; Lim, Jasmine 86   VIAFID ORCID Logo  ; Soo-Hwang, Teo 87 ; Lin, Daniel W 88 ; Newcomb, Lisa F 88 ; Lessel, Davor 89 ; Gamulin, Marija 90 ; Kulis, Tomislav 91 ; Kaneva, Radka 92 ; Usmani, Nawaid 93 ; Slavov, Chavdar 94 ; Mitev, Vanio 92 ; Parliament, Matthew 93 ; Singhal, Sandeep 95 ; Claessens, Frank 96 ; Joniau, Steven 97 ; Van den Broeck, Thomas 98 ; Larkin, Samantha 99 ; Townsend, Paul A 100 ; Aukim-Hastie, Claire 101 ; Gago-Dominguez, Manuela 102 ; Jose Esteban Castelao 103 ; Martinez, Maria Elena 104 ; Roobol, Monique J 105 ; Jenster, Guido 105 ; Ron H N van Schaik 106 ; Menegaux, Florence 107 ; Truong, Thérèse 107   VIAFID ORCID Logo  ; Koudou, Yves Akoli 107 ; Xu, Jianfeng 108   VIAFID ORCID Logo  ; Kay-Tee Khaw 109 ; Cannon-Albright, Lisa 110 ; Pandha, Hardev 101 ; Michael, Agnieszka 101 ; Kierzek, Andrzej 101 ; Thibodeau, Stephen N 111 ; McDonnell, Shannon K 112 ; Schaid, Daniel J 112 ; Lindstrom, Sara 113 ; Turman, Constance 114 ; Ma, Jing 62 ; Hunter, David J 114 ; Riboli, Elio 115 ; Siddiq, Afshan 116 ; Canzian, Federico 117 ; Kolonel, Laurence N 118 ; Loic Le Marchand 118 ; Hoover, Robert N 6 ; Machiela, Mitchell J 6 ; Kraft, Peter 114 ; Cook, Margaret 119 ; Thwaites, Alison 1 ; Guy, Michelle 1 ; Whitmore, Ian 1 ; Morgan, Angela 1 ; Fisher, Cyril 1 ; Hazel, Steve 1 ; Livni, Naomi 1 ; Spurdle, Amanda 120 ; Srinivasan, Srilakshmi 13 ; Mary-Anne Kedda 13 ; Aitken, Joanne 14 ; Gardiner, Robert 121 ; Hayes, Vanessa 122 ; Butler, Lisa 123 ; Taylor, Renea 124 ; Yeadon, Trina 13 ; Eckert, Allison 13 ; Saunders, Pamela 125 ; Haynes, Anne-Maree 126 ; Papargiris, Melissa 124 ; Kujala, Paula 127 ; Talala, Kirsi 128 ; Murtola, Teemu 129 ; Taari, Kimmo 130 ; Dearnaley, David 131 ; Barnett, Gill 30 ; Bentzen, Søren 132 ; Elliott, Rebecca 28 ; Ranu, Hardeep 31 ; Hicks, Belynda 133 ; Vogt, Aurelie 133 ; Hutchinson, Amy 134 ; Cox, Angela 135 ; Davis, Michael 38 ; Brown, Paul 42 ; George, Anne 136 ; Marsden, Gemma 39 ; Lane, Athene 38 ; Lewis, Sarah J 38 ; Berry, Clare 115 ; Kulkarni, Girish S 42 ; Toi, Ants 137 ; Evans, Andrew 138 ; Zlotta, Alexandre R 42 ; Theodorus H van der Kwast 138 ; Imai, Takashi 139 ; Saito, Shiro 140 ; Marzec, Jacek 46 ; Cao, Guangwen 47 ; Lin, Ji 47 ; Ling, Jin 47 ; Li, Meiling 47 ; Shan-Chao, Zhao 141 ; Ren, Guoping 142 ; Yu, Yongwei 143 ; Wu, Yudong 144 ; Wu, Ji 145 ; Zhou, Bo 146 ; Zhang, Yangling 142 ; Li, Jie 147 ; He, Weiyang 147 ; Guo, Jianming 50 ; Pedersen, John 148 ; Hopper, John L 149 ; Milne, Roger 52 ; Klim, Aleksandra 32 ; Carballo, Ana 57 ; Lobato-Busto, Ramón 150 ; Peleteiro, Paula 57 ; Calvo, Patricia 57 ; Aguado, Miguel 56 ; Ruiz-Dominguez, José Manuel 151 ; Cecchini, Lluís 152 ; Mengual, Lourdes 153 ; Alcaraz, Antonio 154 ; Bustamante, Mariona 155 ; Gracia-Lavedan, Esther 60 ; Dierssen-Sotos, Trinidad 61 ; Gomez-Acebo, Ines 61 ; Pow-Sang, Julio 156 ; Park, Hyun 63 ; Babu Zachariah 63 ; Kluzniak, Wojciech 66 ; Kolb, Suzanne 68 ; Klarskov, Peter 71 ; Stegmaier, Christa 76 ; Vogel, Walther 77 ; Herkommer, Kathleen 157 ; Bohnert, Philipp 78 ; Maia, Sofia 82 ; Silva, Maria P 82 ; De Langhe, Sofie 84 ; Thierens, Hubert 84 ; Tan, Meng H 86 ; Ong, Aik T 86 ; Kastelan, Zeljko 91 ; Popov, Elenko 94 ; Kachakova, Darina 92 ; Mitkova, Atanaska 92 ; Vlahova, Aleksandrina 158 ; Dikov, Tihomir 158 ; Christova, Svetlana 158 ; Carracedo, Angel 159 ; Bangma, Christopher 105 ; Schroder, F H 105 ; Cenee, Sylvie 160 ; Tretarre, Brigitte 161 ; Rebillard, Xavier 162 ; Mulot, Claire 163 ; Sanchez, Marie 160 ; Adolfsson, Jan 164 ; Stattin, Par 165 ; Johansson, Jan-Erik 166 ; Cavalli-Bjoerkman, Carin 18 ; Karlsson, Ami 101 ; Broms, Michael 101 ; Wu, Huihai 101 ; Tillmans, Lori 111 ; Riska, Shaun 111 ; Freedman, Matthew 167 ; Wiklund, Fredrik 18 ; Chanock, Stephen 6 ; Henderson, Brian E 8 ; Easton, Douglas F 21   VIAFID ORCID Logo  ; Haiman, Christopher A 8 ; Eeles, Rosalind A 131   VIAFID ORCID Logo  ; Conti, David V 8 ; Kote-Jarai, Zsofia 1 

 The Institute of Cancer Research, London, UK 
 MRC Biostatistics Unit, University of Cambridge, Cambridge, UK 
 The Institute of Cancer Research, London, UK; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK 
 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 
 Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA; Seidman Cancer Center, University Hospitals, Cleveland, OH, USA 
 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA 
 The Institute of Cancer Research, London, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK 
 Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA 
 Institute of Population Health, University of Manchester, Manchester, UK; Warwick Medical School, University of Warwick, Coventry, UK 
10  Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA 
11  SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 
12  CHRISTUS Santa Rosa Hospital - Medical Center, San Antonio, TX, USA 
13  Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, Australia; Translational Research Institute, Brisbane, QLD, Australia 
14  Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia; Cancer Council Queensland, Fortitude Valley, QLD, Australia 
15  Chris O’Brien Lifehouse (COBLH), Camperdown, Sydney, NSW, Australia; Garvan Institute of Medical Research, Sydney, NSW, Australia 
16  Dame Roma Mitchell Cancer Research Centre, University of Adelaide, Adelaide, SA, Australia 
17  Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia; Prostate Cancer Translational Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia 
18  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden 
19  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Urology, Karolinska University Hospital, Stockholm, Sweden 
20  Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden 
21  Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, UK 
22  Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, UK; Department of Applied Health Research, University College London, London, UK 
23  Institute of Biomedicine, University of Turku, Turku, Finland; Tyks Microbiology and Genetics, Department of Medical Genetics, Turku University Hospital, Turku, Finland 
24  Department of Urology, Tampere University Hospital, University of Tampere, Tampere, Finland 
25  Institute of Biomedicine, University of Turku, Turku, Finland 
26  Department of Epidemiology, School of Health Sciences, University of Tampere, Tampere, Finland 
27  Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 
28  Division of Cancer Sciences, Manchester Academic Health Science Centre, Radiotherapy Related Research, Manchester NIHR Biomedical Research Centre, The Christie Hospital NHS Foundation Trust, University of Manchester, Manchester, UK 
29  Centre for Cancer Genetic Epidemiology, Department of Oncology, Strangeways Laboratory, University of Cambridge, Cambridge, UK 
30  University of Cambridge Department of Oncology, Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 
31  Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA 
32  Washington University School of Medicine, St. Louis, MO, USA 
33  GRC N°5 ONCOTYPE-URO, UPMC Univ Paris 06, Tenon Hospital, Paris, France; CeRePP, Tenon Hospital, Paris, France 
34  Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark 
35  Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark; Department of Urology, Aarhus University Hospital, Aarhus N, Denmark 
36  Department of Medical Genetics, Oslo University Hospital, Oslo, Norway 
37  Department of Oncology, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK 
38  School of Social and Community Medicine, University of Bristol, Bristol, UK 
39  Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Faculty of Medical Science, John Radcliffe Hospital, University of Oxford, Oxford, UK 
40  School of Social and Community Medicine, University of Bristol, Bristol, UK; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK; National Institute for Health Research (NIHR) Biomedical Research Centre, University of Bristol, Bristol, UK 
41  Cancer Epidemiology, Nuffield Department of Population Health, University of Oxford, Oxford, UK 
42  Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada 
43  Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA 
44  Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, USA 
45  Professor of Pathology and Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA 
46  Centre for Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Queen Mary University of London, London, UK 
47  Second Military Medical University, Shanghai, P. R. China 
48  Wuxi Second Hospital, Nanjing Medical University, Wuxi, Jiangzhu, China 
49  Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; The People’s Hospital of Liaoning Province and The People’s Hospital of China Medical University, Shenyang, China 
50  Department of Urology, Zhongshan Hospital, Fudan University Medical College, Shanghai, China 
51  The People’s Hospital of Liaoning Province and The People’s Hospital of China Medical University, Shenyang, China 
52  Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia 
53  Precision Medicine, School and Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia 
54  Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia 
55  Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA 
56  Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain 
57  Department of Radiation Oncology, Complexo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain 
58  Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK; Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain 
59  Division of Family Medicine, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Stockholm, Sweden; Scandinavian Development Services, Danderyd, Sweden 
60  Centre for Research in Environmental Epidemiology (CREAL), Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain 
61  CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; University of Cantabria-IDIVAL, Santander, Spain 
62  Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA 
63  Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA 
64  School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA 
65  Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA 
66  International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland 
67  National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA 
68  Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 
69  Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark 
70  Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark 
71  Department of Urology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark 
72  Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Herlev, Denmark 
73  Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Herlev, Denmark 
74  Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany 
75  Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany 
76  Saarland Cancer Registry, Saarbrücken, Germany 
77  Institute for Human Genetics, University Hospital Ulm, Ulm, Germany 
78  Department of Urology, University Hospital Ulm, Ulm, Germany 
79  Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
80  Cancer Prevention Institute of California, Fremont, CA, USA; Department of Health Research & Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA 
81  Department of Genetics, Portuguese Oncology Institute of Porto, Porto, Portugal; Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal 
82  Department of Genetics, Portuguese Oncology Institute of Porto, Porto, Portugal 
83  Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA 
84  Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium 
85  Department of Radiotherapy, Ghent University Hospital, Gent, Belgium 
86  Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 
87  Cancer Research Malaysia (CRM), Outpatient Centre, Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia 
88  Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Urology, University of Washington, Seattle, WA, USA 
89  Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 
90  Division of Medical Oncology, Urogenital Unit, Department of Oncology at the University Hospital Centre Zagreb, Zagreb, Croatia 
91  Department of Urology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia 
92  Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria 
93  Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; Division of Radiation Oncology, Cross Cancer Institute, Edmonton, AB, Canada 
94  Department of Urology and Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria 
95  Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada 
96  Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium 
97  Department of Urology, University Hospitals Leuven, Leuven, Belgium 
98  Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium 
99  Southampton General Hospital, The University of Southampton, Southampton, UK 
100  Manchester Cancer Research Centre, Faculty of Biology Medicine & Health, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Health Innovation Manchester, University of Manchester, Manchester, UK 
101  The University of Surrey, Guildford, Surrey, UK 
102  Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS, Santiago de Compostela, Spain; Moores Cancer Center, University of California San Diego, La Jolla, CA, USA 
103  Genetic Oncology Unit, CHUVI Hospital, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica Galicia Sur (IISGS), Vigo (Pontevedra), Spain 
104  Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA 
105  Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands 
106  Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands 
107  Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France 
108  Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL, USA 
109  Clinical Gerontology Unit, University of Cambridge, Cambridge, UK 
110  Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA 
111  Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 
112  Division of Biomedical Statistics & Informatics, Mayo Clinic, Rochester, MN, USA 
113  Department of Epidemiology, University of Washington, Seattle, WA, USA 
114  Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 
115  Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK 
116  Genomics England, Queen Mary University of London, London, UK 
117  Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany 
118  Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA 
119  Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK 
120  Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Institute of Medical Research, Herston, QLD, Australia 
121  School of Medicine, University of Queensland, Herston, QLD, Australia; Royal Brisbane & Women’s Hospital, Herston, QLD, Australia 
122  The Kinghorn Cancer Centre (TKCC), Victoria, NSW, Australia 
123  Prostate Cancer Research Group, South Australian Health & Medical Research Institute, Adelaide, SA, Australia 
124  Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, VIC, Australia 
125  University of Adelaide, North Terrace, Adelaide, SA, Australia 
126  Garvan Institute of Medical Research, Sydney, NSW, Australia; The Kinghorn Cancer Centre (TKCC), Victoria, NSW, Australia 
127  Fimlab Laboratories, Tampere University Hospital, Tampere, Finland 
128  Finnish Cancer Registry, Helsinki, Finland 
129  Department of Urology, Tampere University Hospital, University of Tampere, Tampere, Finland; Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland 
130  Department of Urology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland 
131  The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK 
132  Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA 
133  Cancer Genomics Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, FNLCR Leidos Biomedical Research, National Cancer Institute, Frederick, MD, USA 
134  DNA Extraction and Staging Laboratory (DESL), Cancer Genomics Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, FNLCR Leidos Biomedical Research, National Cancer Institute, Frederick, MD, USA 
135  Sheffield Institute for Nucleic Acids, University of Sheffield, Sheffield, UK 
136  Cambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 
137  Department of Medical Imaging, University Health Network, Toronto, ON, Canada 
138  Department of Pathology, University Health Network, Toronto, ON, Canada 
139  Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan 
140  Department of Urology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan 
141  Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China 
142  Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, China 
143  Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai, China 
144  Department of Urology, First Affiliated Hospital, Medical College, Zhengzhou University, Zhengzhou, China 
145  Department of Urology, North Sichuan Medical College, Nanchong, China 
146  Department of Nutrition Science, Shenyang Medical College, Shenyang, China 
147  Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China 
148  Tissupath Pty Ltd., Melbourne, VIC, Australia 
149  Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia 
150  Department of Medical Physics, Complexo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain 
151  Urology Department, Hospital Germans Trias I Pujol, Barcelona, Spain 
152  IMIM (Hospital del Mar Research Institute), Barcelona, Spain 
153  Laboratory and Department of Urology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain; Centre de Recerca Biomèdica CELLEX, Barcelona, Spain 
154  Department and Laboratory of Urology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain 
155  Centre for Research in Environmental Epidemiology (CREAL), Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain 
156  Genitourinary Program, Moffitt Cancer Center, Tampa, FL, USA 
157  Department of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany 
158  Department of General and Clinical Pathology and Alexandrovska University Hospital, Medical University, Sofia, Bulgaria 
159  Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica, CIBERER, IDIS, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; Grupo de Medicina Xenómica, CIBERER, CIMUS, Universidad de Santiago de Compostela, Avenida de Barcelona, Santiago de Compostela, Spain 
160  Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France; Paris-Sud University, UMRS 1018, Villejuif, France 
161  Hérault Cancer Registry, Montpellier, France 
162  Urology Department, Clinique Beau Soleil, Montpellier, France 
163  INSERM U1147, Paris, France 
164  Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Swedish Agency for Health Technology Assessment and Assessment of Social Services, Stockholm, Sweden 
165  Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden 
166  Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden 
167  Dana-Farber Cancer Institute, Boston, MA, USA 
Pages
1-19
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2053312758
Copyright
© 2018. 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.