Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Rosalind A. Eeles, Zsofia Kote-Jarai, Johanna Schleutker, Douglas F. Easton, Prasad Bollina, Sue Bonnington, Debbie Cooper, Andrew Doble, Alan Doherty, Garrett Durkan, Emma Elliott, David Gillatt, Pippa Herbert, Freddie C. Hamdy, Peter Holding, Joanne Howson, Mandy Jones, Roger Kockelbergh, Howard Kynaston, Teresa Lennon & 672 others Norma Lyons, Hing Leung, Hilary Moody, Philip Powell, David E. Neal, Stephen Prescott, Pauline Thompson, Cyril Fisher, Charles Jameson, Sandra Barrett, Penelope Kelham, Paul M. Brown, Anne George, Gemma Marsden, Michael Davis, Jenny L. Donovan, David M. A. Wallace, R. I. Bhatt, K. Subramonian, John Arrand, Louise Flanagan, Sita Ann Bradley, John Pedersen, Charmaine Smith, Melisa Bagnato, Colleen Nelson, Janet L. Stanford, Tracy O'Mara, Kimberly Hinze, Patrica VandenBergh, Beth Newman, David Nicol, John Yaxley, Megan Ferguson, James Stankovich, Russell Thomson, Simon Foote, Elaine A. Ostrander, David Challis, John McArdle, James McKay, Annette Banks, Rebekah McWhirter, Kate Butorac, Heidi Smark, Leigh Blizzard, Elenko Popov, Darina Kachakova, Sue A. Ingles, Rumjana Dodova, Olga Belcheva, Momchil Nikolov, Vanio Mitev, Aleksandrina Vlahova, Tihomir Dikov, Svetlana Christova, Nancy Hamel, Kimberley Kotar, Jian-Guo Hou, Esther M. John, Dan-Feng Xu, Wen-Jun Chang, Xing-Xing Xu, Ulf-Håkan Stenman, Henna Mattila, Sanna Siltanen, Sanna Pakkanen, Jarkko Isotalo, Mika Matikainen, Harald Surowy, Stephen N. Thibodeau, Margot Brugger, Irina Wiest, Bärbel Weber, Kathleen Herkommer, Thomas Paiss, Rainer Kuefer, Natalia Dubrowinskaja, Christoph von Klot, Markus Kuczyk, Peter Hillemanns, Daniel Schaid, Michael Bremer, Johann H. Karstens, Stefan Machtens, Cédric Biedermann, Hans-Ulrich Peter, Nicolas Defabiani, Sabine Bieri, Christophe Girardet, Isabelle Konzelmann, Michèle Stalder, Ali Amin Al Olama, Jong Y. Park, Marie-Mathilde Meier, Liang Wang, Julie Cunningham, Kimberly A. Zuhlke, Emilie K. Johnson, James E. Montie, Babu Zakariah, Hyun Y. Park, Selina Radein, Maria Rincon, Amanda Spurdle, Babu Zachariah, Charnita Zeigler-Johnson, Elaine Spangler, Margerie Coomes, Stephen Gallagher, Amy Walker, N. P. Cohen, I. Conn, Kuchibhotla S. Swami, Leslie E. F. Moffat, Judith Clements, Sue Kenwrick, Helen Patterson, Katherine Waite, Vicki Wiles, C. Irwin, M. Lancashire, B. W. Ellis, Ravi Kulkarni, Riza Murat Gurun, Graham W. Hollins, Joanne L. Dickinson, Rana Mahmood, Robert N. Meddings, Tim Briggs, Irene Chong, James S. Gelister, Faiz Mumtaz, Ramachandran Ravi, Peter R. Malone, A. Pengelly, David Dodds, Christiane Maier, C. Featherston, David Hendry, Gareth Jones, David Kirk, John M. Russell, M. Siva, Mary Leader, Robert J. Thomas, Patrick Morrison, Joe O'Sullivan, Walther Vogel, L. Shum, D. Stewart, Jeremy Feggetter, J. O'Brien, Trevor Cole, Dorthe Cruger, E. R. Maher, Donald Neilson, G. D. Wemyss-Holden, Shabbir Susnerwala, Thilo Dork, Amit Bahl, Raj Persad, Mark Wright, Angelika Zang, Priscilla Leone, Saad Tahir, Omi Parikh, Jaspal Virdi, Victor Izegbu, James Bellringer, Timothy R. Rebbeck, Alison Falconer, Simon Carter, D. Hrouda, Stephen J. Karp, Mark Bower, Michael Dinneen, Cathryn Brock, Hugh Gilbert, P. Jenkins, Kathleen A. Cooney, Nigel R. Boucher, Michael J. James, Richard Cowan, D. Gareth Evans, Jacqueline Livsey, John Logue, James P. Wylie, Fiona Lalloo, Elaine Sugden, Simon F. Brewster, Lisa Cannon-Albright, David J. Cole, C. Connell, Andrew Protheroe, M. F. Saxby, P. G. Ryan, David Peake, M. Coe, R. D. Errington, A. Ibrahim, Isabel Syndikus, Graham G. Giles, Pierre O. Chappuis, C. M. Booth, John Corr, Michael Lynch, P. S. Callaghan, R. Plail, D. Ash, C. Coyle, David Bottomley, Christopher Powell, Christopher Chilton, Pierre Hutter, Mike Henley, A. M. Peracha, John H. Williams, Simon Williams, D. Muthukumar, Stephen A. Thomas, Andrew J. Dickinson, John Hammonds, Paul McInerney, Sarah Pascoe, Maurice Zeegers, Henry Sells, C. J. Tyrell, Stuart F. Tindall, N. Afzal, Steven Andrews, Andrew J. Cornaby, J. A. A. Archbold, Ian H. Kunkler, A. Folkes, Julian Money-Kyrle, Radka Kaneva, N. A. Bax, W. T. Lawrence, F. McKinna, Peter R. Rimington, Chris Dawson, F. Khan, C. Charig, Pieter J. Le Roux, Michael Hehir, Michael F. Smith, Hong-Wei Zhang, James Tweedle, James Glenister, C. D. Eden, Stephen E. M. Langley, Bruce Montgomery, Harry Naerger, Edward Palfrey, Richard Wilson, Khaver N. Qureshi, Ike Apakama, Yong-Jie Lu, Krishna Prasad, Dr. Al-Samerraie, Louise Emmerson, A. Nethersell, Mr. Srinivasan, John Glaholm, Hemant Ohja, Nazeer Dahar, Pallon Daruwala, Rupert Beck, William D. Foulkes, John W. Iacovou, Peter Harper, Matthew Perry, Rick Popert, D. Cahill, H. Jane Dobbs, Louise Izatt, Tim S. O'Brien, Dr. Tong, Anand R. Kelkar, Dallas R. English, J. H. Waxman, David Badenoch, Neil O'Donoghue, Pravin Singh, Anne Lawson, M. Pancharatnam, Nihil Shah, Graham M. Sole, A. J. Pope, Noel W. Clarke, Daniel A. Leongamornlert, Michael Ferro, John M. Harney, S. Fiona Douglas, G. Banerjee, P. Donaldson, Christopher Scrase, David Chadwick, P. D. John Hardman, John R. Hindmarsh, Gokarakonda Suresh, Malgorzata Tymrakiewicz, Natasha Mithal, Keith W. Murray, Owen W. Davison, D. Baxter-Smith, Hanif Motiwala, N. Barber, Gordon Muir, Robert F. Copland, John Dick, Roland Morley, Michelle Guy, Jonathan Morrison, Paul C. Butterworth, Thomas R. L. Griffiths, David Osborn, T. Terry, Julian Barwell, Richard C. Trembath, Pradip Javle, Pradip Basu, I. Mark, Miguel Panades, Audrey T. Ardern-Jones, Thiagarajan Sreenivasan, Damien C. Hanbury, T. A. McNicholas, S. Davidson, David Holden, Siva Namasivayam, Paul J. Reddy, Sharon Beesley, Trevor F. Ford, J. Lewis, Amanda L. Hall, Anula D. Chetiyawardana, James Smith, Gulzar Mufti, Henry Andrews, E. M. Walker, Iqbal Anjum, Pradeep Bose, Malcolm G. Lucas, Richard F. U. Ashford, Jeanette Dickson, Lynne T. O'Brien, Peter Hoskin, Rob Hughes, Peter Ostler, Mark J. Churn, Peter Cooke, John A. Inglis, N. H. Philp, Brian Waymont, Rhona McMenemin, I. Pedley, Rosemary A. Wilkinson, J. Trevor Roberts, J. O. Lee, Edwin T. S. Ho, Stuart Irving, Robert Mills, Krishna K. Sethia, Ralph J. Webb, Denise J. Sheehan, Douglas G. Barnes, Wai-Man Chow, Edward J. Saunders, C. B. Costello, Christine Elwell, Jeremy Elkabir, D. Fermont, A. David Mee, M. Bishop, O. Cole, D. R. Harriss, R .John Lemburger, Michael Sokal, Elizabeth C. Page, Santhanam Sundar, Michael Dunn, Graeme H. Urwin, Richard Benson, Dr. Baria, Mr. Memon, C. Shekhar Biyani, Tony J. Browning, Michael Murphy, S. K. Sundaram, Emma J. Sawyer, P. M. T. Weston, Thomas D. Goode, Tamas Hickish, Bruce M. Castle, Mr. Cummings, Diana Eccles, N. Harvey-Hills, Diana Mort, Pravin Menzes, Munir Ahmed, Stephen M. Edwards, Guy Dawkins, A. El-Modir, Michael Hughes, C. J. Luscombe, N. James, S. J. Hampson, Stephanie Gibbs, P. Chakraborti, M. Kumar, D. Whillis, David P. Dearnaley, Mohamed Kourah, Bohdan T. Parys, Maurice W. Lau, Richard Brown, Derek Fawcett, P. B. Rogers, L. Lee, Gillian E. Mobb, Michalakis L. Pantelides, F. James Bramble, Gianluca Severi, Alan Horwich, Sue Brock, Charles J. M. Carter, Joseph Davies, Donna McBride, John Rundle, Andrew Wedderburn, Matthew Collinson, Robert Cox, R. Ellis, R. Newton, Robert A. Huddart, J. S. O'Rourke, Alastair H. Thomson, Duncan Wheatley, Mark A. Stott, Richard D. Pocock, Julia Rankin, Malcolm Crundwell, Amir Kaisary, Katharine Pigott, Christopher A. Bates, Vincent S. Khoo, Gail Beese, W. G. Bowsher, Adam C. Carter, Richard L. Gower, John Anderson, G. S. M. Harrison, Andrew Adamson, Peter Duffy, Carl Rowbotham, K. A. Woolfenden, Christopher C. Parker, P. A. Cornford, E. Bancroft, Sameer Jhavar, Imogen Locke, Anita Mitra, Sue Shanley, Chris Wynne, Neerah K. Sharma, Alison Birtle, Moeketsi Mokete, Nicholas Van As, Narasimhan Ragavan, Graham Read, M. E. Watson, Marcus Wise, Rosemary Blades, Shyam Matenhelia, Christopher Beacock, Andrew W. S. Elves, Narayanan N. Srihari, Brian Birch, Christopher J. Woodhouse, Catherine M. Heath, Robert Laing, David J. Bloomfield, C. Coker, George P. Deutsch, Matthew Fletcher, T. R. Larner, Shirley Murrell, Jan Nawrocki, Angus Robinson, Alan Thompson, Marie Wilkins, Olivera Frim, Christopher Gallegos, Graham P. Howell, Jonathan McFarlane, Hugh Newman, Ali Samanci, Alister Campbell, Peter J. Guy, Gregor McIntosh, Tim Christmas, C. Hamilton, Simon Hawkyard, Andrew Robertson, L. Coombs, Sanjay Dixit, Sean B. Morris, Andrew J. Ball, T. W. Carr, O. Koreich, Richard Lodge, Chris Ogden, J. W. Prejbisz, Anne C. Robinson, Paul H. Abrams, Mr. Corolis, Mr. Drake, John Graham, Edward Rowe, F. X. Keeley, John McGrath, Hartwig Schwaibold, Colin S. Cooper, Sean Vesey, A. Thurston, Nicholas A. Watkin, F. I. Chinegwundoh, A. Lee, Graeme H. M. Mair, Vinod Nargund, Tim Oliver, P. Nicholas Plowman, Ken Anson, Kenneth Muir, Melissa C. Southey, Shirley Hodgson, Anand K. Saggar, M. J. Bailey, E. M. Gordon, John W. Taylor, P. J. R. Boyd, Chris R. Jones, Roger Walker, Shelagh Joss, P. Whelan, Artitaya Lophatananon, F. Aparcia, Liz Hudson, Anup Patel, Simon A. V. Holmes, W. D. Dunsmuir, Ronald P. Beaney, Frances Calman, Jonathan M. Glass, R. Simcock, R. Lester James, Jo-Fen Liu, Y. Rao, John E. Scoble, A. Adeyoju, Stephen Brown, Gerald Collins, Neil Oakley, P. O'Reilly, S. Lloyd, Christopher Alcock, Jonathan Greenland, Laurence N. Kolonel, Damian Green, Richard Brough, P. J. O'Boyle, Ruaraidh P. Macdonagh, Mark J. Speakman, John Violet, Amir H. Mostafid, Roger S. Kirby, Magdi M. Kirollos, Anna Lydon, Loic Le Marchand, James P. A. MacDermott, Robert Mason, Dawn M. Carnell, Mark Emberton, Stephen J. Harland, E. O'Donoghue, Heather Payne, Gill M. Duchesne, A. R. E. Blacklock, Ken M. Desai, Tiina Wahlfors, Robert Grieve, Caroline Humber, Rajagopalan Sriram, Andrew Stockdale, Michael Willis, Jane Worlding, Karen Bailey, Alexandra Murray, Shibendra Datta, Owen Hughes, Teuvo L. Tammela, Philip N. Matthews, Jim Barber, Jason Lester, M. D. Mason, Kathryn Rowley, Owen Tilsley, Mark Longmuir, Lee Q. Robinson, David A. Jones, D. Christopher Lewis, Anssi Auvinen, John R. Strachan, John C. Crisp, S. Mitchell, Elizabeth Sherwin, Duncan McLaren, David N. Tulloch, C. Ferguson, Peter Kirkbride, O. Karim, Sarah J. Lewis, Marc Laniado, T. Philp, Paula Wells, Ralph Beard, Thomas Liston, Simon Woodhams, Alan R. De Bolla, J. P. Kelleher, Andrew Weaver, Christopher H. Parker, Angela Cox, Tim Porter, M. J. Stower, J. R. Wilson, Ernest K. N. Ahiaku, John L. Hopper, Liesel M. Fitzgerald, Joseph S. Koopmeiners, Danielle M. Karyadi, Erika M. Kwon, Mariana C. Stern, Roman Corral, Amit D. Joshi, Ahva Shahabi, Shannon K. McDonnell, Thomas A. Sellers, Brian E. Henderson, Julio Pow-Sang, Suzanne Chambers, Joanne Aitken, R. A. (Frank) Gardiner, Jyotsna Batra, Mary Anne Kedda, Felicity Lose, Andrea Polanowski, Briony Patterson, Jürgen Serth, Christopher A. Haiman, Andreas Meyer, Manuel Luedeke, Klara Stefflova, Anna M. Ray, Ethan M. Lange, Jim Farnham, Humera Khan, Chavdar Slavov, Atanaska Mitkova, Guangwen Cao

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Abstract

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10⁻⁸ to P = 2.7 x 10⁻³³).
Original languageEnglish
Pages (from-to)1116-1121
Number of pages6
JournalNature Genetics
Volume41
Issue number10
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Eeles, R. A., Kote-Jarai, Z., Schleutker, J., Easton, D. F., Bollina, P., Bonnington, S., ... Cao, G. (2009). Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nature Genetics, 41(10), 1116-1121. https://doi.org/10.1038/ng.450