Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Zsofia Kote-Jarai, Ali Amin Al Olama, Graham G. Giles, Gianluca Severi, Johanna Schleutker, Maren Weischer, Daniele Campa, Elio B Riboli, Tim J. Key, Henrik Gronberg, David J. Hunter, Peter Kraft, Michael J Thun, Sue A. Ingles, Stephen J Chanock, Demetrius Albanes, Richard B Hayes, David E. Neal, Freddie C Hamdy, Jenny L. DonovanPaul D P Pharoah, Fredrick Schumacher, Brian E Henderson, Janet L. Stanford, Elaine A. Ostrander, Karina Dalsgaard Sorensen, Thilo Dörk, Gerald L Andriole, Joanne L Dickinson, Cezary Cybulski, Jan Lubinski, Amanda B Spurdle, Judith A. Clements, Suzanne Chambers, Joanne Aitken, R. A.Frank Gardiner, Stephen N. Thibodeau, Dan Schaid, Esther M. John, Christiane Maier, Walther Vogel, Kathleen A. Cooney, Jong Y. Park, Lisa Cannon-Albright, Hermann Brenner, Tomonori Habuchi, Wei-Hong Zhang, Yong Jie Lu, Radka P. Kaneva, Ken Muir, Sara Benlloch, Daniel A. Leongamornlert, Edward J. Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Lynne T O'Brien, Rosemary A Wilkinson, Amanda L Hall, Emma J. Sawyer, Tokhir Dadaev, Jonathan Morrison, David P Dearnaley, Alan Horwich, Robert A Huddart, Vincent S. Khoo, Christopher Parker, Nicholas Van As, Christopher J. Woodhouse, Alan Thompson, Tim Christmas, Chris Ogden, Colin S Cooper, Aritaya Lophatonanon, Melissa C. Southey, John L. Hopper, Dallas R. English, Tiina Wahlfors, Teuvo L.J. Tammela, Peter Klarskov, Børge G. Nordestgaard, M. Andreas Røder, Anne Tybjarg-Hansen, Stig E Bojesen, Ruth C Travis, Federico Canzian, Rudolf J Kaaks, Fredrik Wiklund, Markus Aly, Sara Lindstrom, William Ryan Diver, Susan M. Gapstur, Mariana C. Stern, Roman Corral, Jarmo Virtamo, Angela Cox, Christopher A Haiman, Loic Le Marchand, Liesel M. Fitzgerald, Suzanne Kolb, Erika M. Kwon, Danielle M. Karyadi, Torben Falck Ørntoft, Michael Borre, Andreas Meyer, Jürgen Serth, Meredith Yeager, Sonja I. Berndt, James R Marthick, Briony Patterson, Dominika Wokolorczyk, Jyotsna Batra, Felicity A Lose, Shannon K. McDonnell, Amit D. Joshi, Ahva Shahabi, Antje E. Rinckleb, Ana Ray, Thomas A Sellers, Hui-Yi Lin Lin, Robert A. Stephenson, James Farnham, Heiko Muller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guang Wen Cao, Chavdar Slavov, Vanio Mitev, Douglas F Easton, Rosalind A Eeles

Research output: Contribution to journalArticleResearchpeer-review

228 Citations (Scopus)

Abstract

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10-8 to P = 2.7 × 10-24). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining 425% of the familial risk in this disease, have now been identified.

Original languageEnglish
Pages (from-to)785-791
Number of pages7
JournalNature Genetics
Volume43
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Cite this