Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04

AUTHORS

Edward J Saunders, Tokhir Dadaev, Daniel A Leongamornlert, Ali Amin Al Olama, Sara Benlloch, Graham G Giles, Fredrik Wiklund, Henrik Grönberg, Christopher A Haiman, Johanna Schleutker, Børge G Nordestgaard, Ruth C Travis, David Neal, Nora Pasayan, Kay-Tee Khaw, Janet L Stanford, William J Blot, Stephen N Thibodeau, Christiane Maier, Adam S Kibel, Cezary Cybulski, Lisa Cannon-Albright, Hermann Brenner, Jong Y Park, Radka Kaneva, Jyotsna Batra, Manuel R Teixeira, Hardev Pandha, Koveela Govindasami, Ken Muir, Genetic Prostate Cancer Study Collaborators, Z Abbasi, M Akhlil Abdul-Hamid, Paul D Abel, Paul H Abrams, Fawzi A Adab, Andrew Adamson, A Adeyoju, Naveed Afzal, Ernest K N Ahiaku, Munir Ahmed, Mohammed L Al Sudani, Christopher Alcock, Zulfiqar Ali, David J Almond, Roberto Alonzi, Amir S M Al-Samarraie, Al-Samerraie, Waleed Al-Singary, Al-Sudani, John Anderson, Steven Andrews, Henry Andrews, Iqbal Anjum, Ken Anson, Nicola A Anyamene, Ike Apakama, F Aparcia, J A A Archbold, D Ash, Richard F U Ashford, A Azzabi, David Badenoch, Amit Bahl, M J Bailey, Karen Bailey, Andrew J Ball, G Banerjee, N Barber, Jim Barber, Baria, Douglas G Barnes, J Bashir, Pradip Basu, Christopher A Bates, N A Bax, D Baxter-Smith, Amar Bdesha, Christopher J M Beacock, Ronald P Beaney, Ralph Beard, John D Beatty, Rupert Beck, Gail Beese, Sharon Beesley, C Richard W Bell, James Bellringer, Richard Benson, Beresford, Christopher R A Bevis, Rajanee Bhana, S Bhanot, A Bhatnagar, R I Bhatt, Brian Birch, Alison Birtle, M Bishop, C Shekhar Biyani, A R E Blacklock, Rosemary Blades, Peter Bliss, David J Bloomfield, S Boddy, C M Booth, Pradeep Bose, Michael C Bott, David Bottomley, Nigel R Boucher, J Bowen, Mark Bower, W G Bowsher, P J R Boyd, F James Bramble, Simon F Brewster, Tim Briggs, Cathryn Brock, Sue Brock, Stephen Bromage, Richard Brough, Richard Brown, Stephen Brown, Tony J Browning, N Bryan, Neil A Burgess, Nicholas Burns-Cox, Paul C Butterworth, D Cahill, P S Callaghan, John Calleary, M Calleja, Frances Calman, Philip Camilleri, Alister Campbell, Andrea Cannon, Dawn M Carnell, T W Carr, Simon Carter, Charles J M Carter, Adam C Carter, Bruce M Castle, David Chadwick, Rohit Chahal, P Chakraborti, Chappell, C Charig, Anula D Chetiyawardana, Christopher Chilton, F I Chinegwundoh, Irene Chong, Ananya Choudhury, Wai-Man Chow, Timothy J Christmas, Mark J Churn, Noel W Clarke, Jorge Clavijo-Eisele, M Coe, N P Cohen, C Coker, Trevor Cole, David J Cole, O Cole, Gerald Collins, Matthew Collinson, I Conn, C Connell, Audrey Cook, Peter Cooke, Graeme Cooksey, L Coombs, Robert F Copland, Andrew J Cornaby, P A Cornford, Corolis, John Corr, C B Costello, N Coull, Richard Cowan, Robert Cox, C Coyle, Jeremy Crew, John C Crisp, W Cross, Dorthe Cruger, Malcolm Crundwell, Cummings, Nazeer Dahar, Francis N Daniel, J Darrad, Pallon Daruwala, Gautam Das, Shibendra Datta, S Davidson, Joseph Davies, Owen W Davison, Guy Dawkins, Chris Dawson, Alan R De Bolla, David Dearnaley, Ken M Desai, George P Deutsch, John Dick, Andrew J Dickinson, Jeanette Dickson, Michael Dinneen, Sanjay Dixit, H Jane Dobbs, A Doble, David Dodds, Alan Doherty, P Donaldson, M Dooldeniya, S Fiona Douglas, Drake, Gill M Duchesne, Peter Duffy, Michael Dunn, W D Dunsmuir, Sajid K Durrani, Alan C Eaton, Diane Eccles, B Eddy, C D Eden, J Edwards, Jeremy Elkabir, P Tony Elliott, B W Ellis, R Ellis, A El-Modir, Andrew W S Elves, Christine Elwell, Mark Emberton, Louise Emmerson, Roland C D England, R D Errington, D Gareth Evans, Alison Falconer, Derek Fawcett, C Featherston, Carolyn J Featherstone, Jeremy Feggetter, C Ferguson, D Fermont, Michael Ferro, Matthew Fletcher, A Folkes, Trevor F Ford, Paul W Foster, Kevin N Franks, Olivera Frim, Joanna Gale, Christopher Gallegos, James S Gelister, Ghana, Stephanie Gibbs, Hugh Gilbert, David Gillatt, John Glaholm, Jonathan M Glass, James Glenister, Thomas D Goode, E M Gordon, Richard L Gower, John Graham, Damian Green, Jonathan Greenland, Robert Grieve, Thomas R L Griffiths, Sandy Gujral, Nishi Gupta, Riza Murat Gurun, Peter J Guy, Neil Haldar, N Halder, F C Hamdy, C Hamilton, John Hammonds, S J Hampson, Damien C Hanbury, P D John Hardman, Stephen J Harland, John M Harney, Peter Harper, Sarah Harris, D Harris, G S M Harrison, D R Harriss, N Harvey-Hills, Simon Hawkyard, Catherine M Heath, Michael Hehir, Giles O Hellawell, David Hendry, Mike Henley, Ann Henry, John Hetherington, Tamas Hickish, James A Hicks, Serena Hilman, Richard Hindley, John R Hindmarsh, John Hines, M Hingorani, Edwin T S Ho, Shirley Hodgson, U Hoffman, David Holden, A Hollingdale, Graham W Hollins, Simon A V Holmes, Gail Horan, Alan Horwich, Peter Hoskin, Graham P Howell, D Hrouda, Robert Huddart, Liz Hudson, Rob Hughes, Michael Hughes, Owen Hughes, Caroline Humber, John W Iacovou, A Ibrahim, John A Inglis, Stuart Irving, C Irwin, Louise Izatt, Victor Izegbu, Basharat Jameel, Michael J James, N James, R Lester James, Pradip Javle, P Jenkins, Sameer Jhavar, Gareth Jones, Chris R Jones, David A Jones, J Joseph, Shelagh Joss, Amir Kaisary, Alexandre L Kaliski, G Kapur, O Karim, Stephen J Karp, F X Keeley, Anand R Kelkar, J P Kelleher, John Kelly, Sue Kenwrick, F Khan, Vincent Khoo, Rachel M Kimber, R Kinder, Roger S Kirby, David Kirk, Peter Kirkbride, Magdi M Kirollos, Roger Kockelbergh, Philip C W C Koenig, Gordon G Kooiman, O Koreich, Anthony Koupparis, Mohamed Kourah, Sigurd Kraus, Magda L Kujawa, Ravi Kulkarni, M Kumar, Ian H Kunkler, H Kynaston, Katherine L Lachlan, Robert Laing, Fiona Lalloo, M Lancashire, Stephen E M Langley, Marc Laniado, T R Larner, Maurice W Lau, W T Lawrence, Anne Lawson, Pieter J Le Roux, Mary Leader, J O Lee, L Lee, A Lee, R John Lemburger, Priscilla Leone, Jason Lester, Hing Leung, J Lewis, D Christopher Lewis, Thomas Liston, Jacqueline Livsey, S Lloyd, Imogen Locke, Richard Lodge, John Logue, Mark Longmuir, Malcolm G Lucas, C J Luscombe, Anna Lydon, Michael Lynch, Naing N K Lynn, James P A MacDermott, Ruaraidh P Macdonagh, Macdonald, Sanjeev Madaan, Kudingila R Madhava, Joseph Maguire, E R Maher, Rana Mahmood, Graeme H M Mair, Peter R Malone, Stephen A Mangar, Mark Mantle, I Mark, Robert Mason, M D Mason, Matanhelia, Shyam Matenhelia, Philip N Matthews, J McAleese, Donna McBride, Jonathan McFarlane, McGrath, Craig McIlhenny, Paul McInerney, Gregor McIntosh, F McKinna, Duncan McLaren, Esther McLarty, Rhona McMenemin, Alan McNeill, T A McNicholas, Robert N Meddings, A David Mee, Lucinda Melcher, Memon, Pravin Menzes, Marek Miller, Robert Mills, S Mitchell, Natasha Mithal, Anita Mitra, Gillian E Mobb, Leslie E F Moffat, Mokete, Julian Money-Kyrle, Bruce Montgomery, Martin P Moody, Roland Morley, Sean B Morris, Patrick Morrison, Diana Mort, Amir H Mostafid, Hanif Motiwala, Gulzar Mufti, Gordon Muir, Faiz Mumtaz, Michael Murphy, Keith W Murray, Alexandra Murray, Shirley Murrell, D Muthukumar, Harry Naerger, Siva Namasivayam, Vinod Nargund, Nawrocki, Donald Neilson, A Nethersell, Julian Barwell, Jacqueline C Newby, Hugh Newman, R Newton, Neil Oakley, P J O'Boyle, J O'Brien, Tim S O'Brien, H O'Donnell, Neil O'Donoghue, E O'Donoghue, Chris Ogden, Hemant Ohja, Tim Oliver, Eng K Ong, P O'Reilly, J S O'Rourke, David Osborn, Peter Ostler, Joe O'Sullivan, J Owen, Edward Palfrey, Miguel Panades, Niki Panakis, M Pancharatnam, Michalakis L Pantelides, U Panwar, Omi Parikh, Chris Parker, Christopher H Parker, Bohdan T Parys, Sarah Pascoe, Anup Patel, Joan Paterson, S Pathack, Jhumur Pati, Helen Patterson, Pattu, A Paul, Heather Payne, David Peake, I Pedley, A Pengelly, Amjad M Peracha, Matthew Perry, Raj Persad, John Peters, N H Philp, T Philp, Lisa M Pickering, Katharine Pigott, R Plail, P Nicholas Plowman, Richard D Pocock, A J Pope, Rick Popert, Tim Porter, John M Potter, Christopher Powell, Thomas B Powles, Krishna Prasad, Seshadri Sri Prasad, J W Prejbisz, Stephen Prescott, Andrew Protheroe, Khaver N Qureshi, Nigel Raby, Narasimhan Ragavan, Palaniappa G S Raju, Prakash B Ramachandra, R Raman, Abhay Rane, Julia Rankin, Y Rao, Hari L Ratan, Ramachandran Ravi, K Ravishankar, Read, Paul J Reddy, Peter R Rimington, Peter A Ritchie, J Trevor Roberts, Andrew Robertson, Angus Robinson, Anne C Robinson, Lee Q Robinson, Mark A Rochester, P B Rogers, Tomas P Rosenbaum, Neil Rothwell, Carl Rowbotham, Rowe, Kathryn Rowley, Deborah Ruddy, John Rundle, John M Russell, P G Ryan, A Sabharwal, Anand K Saggar, Ali Samanci, Vijay K Sangar, M F Saxby, Hartwig Schwaibold, John E Scoble, Christopher Scrase, Selim, Henry Sells, Krishna K Sethia, David C Shackley, Shaffer, Nihil Shah, D Shakespeare, Sue Shanley, Neerah K Sharma, Denise J Sheehan, Elizabeth Sherwin, Poh Lin Shum, LucySide, Norma Sidek, Karol Sikora, R Simcock, Andrew M Sinclair, Pravin Singh, M Siva, Michael F Smith, James Smith, Michael Sokal, Graham M Sole, Mark J Speakman, Alexander Spiers, Thiagarajan Sreenivasan, Narayanan N Srihari, Srinivasan, Rajagopalan Sriram, John N Staffurth, D Stewart, Andrew Stockdale, Mark A Stott, M J Stower, John R Strachan, Nicholas S A Stuart, Elaine Sugden, Duncan Summerton, Santhanam Sundar, S K Sundaram, Gokarakonda Suresh, Shabbir Susnerwala, Kuchibhotla S Swami, Stephanie J Symons, Isabel Syndikus, Saad Tahir, J Tanquay, John W Taylor, J W Taylor, T Terry, Robert J Thomas, Stephen A Thomas, Alan Thompson, Alastair H Thomson, A Thurston, Owen Tilsley, Stuart F Tindall, K Tipples, Tong, Hamid Toussi, Elizabeth W Toy, Richard C Trembath, David N Tulloch, Kevin J Turner, James Tweedle, C J Tyrell, N Umez-Eronini, Graeme H Urwin, Justin A Vale, Van As, Nicholas Van As, Subramaniam Vasanthan, Sean Vesey, Maria Vilarino-Varela, John Violet, Jaspal Virdi, Robert Wade, Katherine Waite, E M Walker, Roger Walker, David M A Wallace, Nicholas A Watkin, M E Watson, J H Waxman, Brian Waymont, Andrew Weaver, Ralph J Webb, Andrew Wedderburn, Paula Wells, G D Wemyss-Holden, P M T Weston, Duncan Wheatley, P Whelan, D Whillis, Adam D Wilde, Vicki Wiles, Marie Wilkins, John H Williams, Simon Williams, Michael Willis, Michael I Wills, Richard Wilson, J R Wilson, Mathias H Winkler, Marcus Wise, Simon Woodhams, C Woodhouse, Cathryn Woodward, Woolf, K A Woolfenden, Jane Worlding, Mark Wright, WYLIE, James P Wylie, Chris Wynne, Angelika Zang, A Zarkar, ProtecT Study Collaborators, Angela Cox, Paul M. Brown, Anne George, Gemma Marsden, Athene Lane, Michael Davis, Prasad Bollina, Sue Bonnington, Lynne Bradshaw, James Catto, Debbie Cooper, Liz Down, Andrew Doble, Garrett Durkan, Emma Elliott, Pippa Herbert, Peter Holding, Joanne Howson, Mandy Jones, Rajeev Kumar, Howard Kynaston, Teresa Lennon, Norma Lyons, Malcolm Mason, Hilary Moody, Philip Powell, Alan Paul, Derek Rosario, Patricia OSullivan, Pauline Thompson, Sarah Tidball, The PRACTICAL Consortium, Margaret Cook, Angela Morgan, Artitaya Lophatananon, Cyril Fisher, Malgorzata Tymrakiewicz, Michelle Guy, Rosemary Wilkinson, Sara Jugurnauth-Little, Steve Hazel, Melissa C Southey, Liesel M Fitzgerald, John Pedersen, John Hopper, Ami Karlsson, Carin Cavalli-Bjoerkman, Jan-Erik Johansson, Jan Adolfson, Markus Aly, Michael Broms, Paer Stattin, Brian E Henderson, Fredrick Schumacher, Anssi Auvinen, Kimmo Taari, Liisa Maeaettaenen, Paula Kujala, Teemu Murtola, Teuvo LJ Tammela, Tiina Wahlfors, Andreas Roder, Peter Iversen, Peter Klarskov, Sune F Nielsen, Tim J Key, Hans Wallinder, Sven Gustafsson, Jenny L Donovan, Freddie Hamdy, Paul Brown, Paul Pharoah, Lisa B Signorello, Wei Zheng, Shannon K McDonnell, Daniel J Schaid, Liang Wang, Lori Tillmans, Shaun Riska, Thomas Schnoeller, Kathleen Herkommer, Manuel Luedeke, Walther Vogel, Dominika Wokolorczyk, Jan Lubiski, Wojciech Kluzniak, Katja Butterbach, Christa Stegmaier, Bernd Holleczek, Hui-Yi Lin, Hyun Park, Julio Pow-Sang, Thomas Sellers, Chavdar Slavov, Aleksandrina Vlahova, Atanaska Mitkova, Darina Kachakova, Elenko Popov, Svetlana Christova, Tihomir Dikov, Vanio Mitev, Allison Eckert, Amanda Spurdle, Angus Collins, Glenn Wood, Greg Malone, Judith A Clements, Kris Kerr, Megan Turner, Pamela Saunders, Peter Heathcote, Srilakshmi Srinivasan, Leire Moya, Trina Yeadon, Joana Santos, Carmen Jerónimo, Paula Paulo, Pedro Pinto, Rui Henrique, Sofia Maia, Agnieszka Michael, Andrzej Kierzek, Huihai Wu, Douglas F Easton, Rosalind A Eeles, Zsofia Kote-Jarai

ABSTRACT

BACKGROUND: Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. METHODS: Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. RESULTS: Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. CONCLUSIONS: MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers. More... »

PAGES

945

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/bjc.2016.50

    DOI

    http://dx.doi.org/10.1038/bjc.2016.50

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1047049332

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26964030


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