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Comparative Study
. 2011 Jul 10;43(8):785-91.
doi: 10.1038/ng.882.

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

Zsofia Kote-Jarai  1 , Ali Amin Al Olama, Graham G Giles, Gianluca Severi, Johanna Schleutker, Maren Weischer, Daniele Campa, Elio Riboli, Tim Key, Henrik Gronberg, David J Hunter, Peter Kraft, Michael J Thun, Sue Ingles, Stephen Chanock, Demetrius Albanes, Richard B Hayes, David E Neal, Freddie C Hamdy, Jenny L Donovan, Paul Pharoah, Fredrick Schumacher, Brian E Henderson, Janet L Stanford, Elaine A Ostrander, Karina Dalsgaard Sorensen, Thilo Dörk, Gerald Andriole, Joanne L Dickinson, Cezary Cybulski, Jan Lubinski, Amanda 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, Hong-Wei Zhang, Yong-Jie Lu, Radka 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 C 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 Tybjærg-Hansen, Stig E Bojesen, Ruth Travis, Federico Canzian, Rudolf Kaaks, Fredrik Wiklund, Markus Aly, Sara Lindstrom, W Ryan Diver, Susan Gapstur, Mariana C Stern, Roman Corral, Jarmo Virtamo, Angela Cox, Christopher A Haiman, Loic Le Marchand, Liesel Fitzgerald, Suzanne Kolb, Erika M Kwon, Danielle M Karyadi, Torben Falck Orntoft, Michael Borre, Andreas Meyer, Jürgen Serth, Meredith Yeager, Sonja I Berndt, James R Marthick, Briony Patterson, Dominika Wokolorczyk, Jyotsna Batra, Felicity Lose, Shannon K McDonnell, Amit D Joshi, Ahva Shahabi, Antje E Rinckleb, Ana Ray, Thomas A Sellers, Hui-Yi 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; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; UK ProtecT Study Collaborators, The Australian Prostate Cancer BioResource; PRACTICAL Consortium
Affiliations
Comparative Study

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

Zsofia Kote-Jarai et al. Nat Genet. .

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 ∼25% of the familial risk in this disease, have now been identified.

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Figures

Figure 1
Figure 1
Forest plots for the 10 SNPs genotyped in stages 1–4. Squares represent the estimated per-allele odds ratio (OR) for individual studies. The area of square is inversely proportional to the precise of the estimate. Diamonds represent the summary OR estimates for the subgroups indicated. Horizontal lines represent 95% confidence limits.
Figure 1
Figure 1
Forest plots for the 10 SNPs genotyped in stages 1–4. Squares represent the estimated per-allele odds ratio (OR) for individual studies. The area of square is inversely proportional to the precise of the estimate. Diamonds represent the summary OR estimates for the subgroups indicated. Horizontal lines represent 95% confidence limits.
Figure 2
Figure 2
Regional plots of four of the associated SNPs at 5p15 (a.), 3q25 (b.), 5p12 (c.), and 6p21 (d.). Plots show the genomic regions associated with PrCa and −log10 association P values of SNPs. Also shown are the SNP build 36/hg18 coordinates in kilobases, recombination rates and genes in the region. The intensity of red shading indicates the strength of LD (r2) with the index SNP. Plots drawn with a modified Rscript from http://www.broadinstitute.org/mpg/snap/ldplot.php
See this image and copyright information in PMC

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