A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

Ali Amin Al Olama, Zsofia Kote-Jarai, Fredrick R. Schumacher, Fredrik Wiklund, Sonja I. Berndt, Sara Benlloch, Graham G. Giles, Gianluca Severi, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, David J. Hunter, Brian E. Henderson, Michael J. Thun, Michael Gaziano, Edward L. Giovannucci, Afshan Siddiq, Ruth C. Travis, David G. Cox, Federico CanzianElio Riboli, Timothy J. Key, Gerald Andriole, Demetrius Albanes, Richard B. Hayes, Johanna Schleutker, Anssi Auvinen, Teuvo L.J. Tammela, Maren Weischer, Janet L. Stanford, Elaine A. Ostrander, Cezary Cybulski, Jan Lubinski, Stephen N. Thibodeau, Daniel J. Schaid, Karina D. Sorensen, Jyotsna Batra, Judith A. Clements, Suzanne Chambers, Joanne Aitken, Robert A. Gardiner, Christiane Maier, Walther Vogel, Thilo Dörk, Hermann Brenner, Tomonori Habuchi, Sue Ingles, Esther M. John, Joanne L. Dickinson, Lisa Cannon-Albright, Manuel R. Teixeira, Radka Kaneva, Hong Wei Zhang, Yong Jie Lu, Jong Y. Park, Kathleen A. Cooney, Kenneth R. Muir, Daniel A. Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Nadiya Mahmud, Michelle Guy, Koveela Govindasami, 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 Dudderidge, Chris Ogden, Colin S. Cooper, Artitaya Lophatonanon, Melissa C. Southey, John L. Hopper, Dallas English, Jarmo Virtamo, Loic Le Marchand, Daniele Campa, Rudolf Kaaks, Sara Lindstrom, W. Ryan Diver, Susan Gapstur, Meredith Yeager, Angela Cox, Mariana C. Stern, Roman Corral, Markus Aly, William Isaacs, Jan Adolfsson, Jianfeng Xu, S. Lilly Zheng, Tiina Wahlfors, Kimmo Taari, Paula Kujala, Peter Klarskov, Børge G. Nordestgaard, M. Andreas Røder, Ruth Frikke-Schmidt, Stig E. Bojesen, Liesel M. FitzGerald, Suzanne Kolb, Erika M. Kwon, Danielle M. Karyadi, Torben Falck Orntoft, Michael Borre, Antje Rinckleb, Manuel Luedeke, Kathleen Herkommer, Andreas Meyer, Jü rgen Serth, James R. Marthick, Briony Patterson, Dominika Wokolorczyk, Amanda Spurdle, Felicity Lose, Shannon K. McDonnell, Amit D. Joshi, Ahva Shahabi, Pedro Pinto, Joana Santos, Ana Ray, Thomas A. Sellers, Hui Yi Lin, Robert A. Stephenson, Craig Teerlink, Heiko Muller, Dietrich Rothenbacher, Norihiko Tsuchiya, Shintaro Narita, Guang Wen Cao, Chavdar Slavov, Vanio Mitev, Stephen Chanock, Henrik Gronberg, Christopher A. Haiman, Peter Kraft, Douglas F. Easton, Rosalind A. Eeles

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significantSNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03-1.21), P = 1.4 × 10-8]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis.

Original languageEnglish (US)
Article numberdds425
Pages (from-to)408-415
Number of pages8
JournalHuman molecular genetics
Volume22
Issue number2
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Al Olama, A. A., Kote-Jarai, Z., Schumacher, F. R., Wiklund, F., Berndt, S. I., Benlloch, S., Giles, G. G., Severi, G., Neal, D. E., Hamdy, F. C., Donovan, J. L., Hunter, D. J., Henderson, B. E., Thun, M. J., Gaziano, M., Giovannucci, E. L., Siddiq, A., Travis, R. C., Cox, D. G., ... Eeles, R. A. (2013). A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease. Human molecular genetics, 22(2), 408-415. [dds425]. https://doi.org/10.1093/hmg/dds425