Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24

Julius Gudmundsson, Patrick Sulem, Andrei Manolescu, Laufey T. Amundadottir, Daniel Gudbjartsson, Agnar Helgason, Thorunn Rafnar, Jon T. Bergthorsson, Bjarni A. Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R. Benediktsdottir, Margret Jakobsdottir, Jianfeng Xu, Thorarinn Blondal, Jelena Kostic, Jielin Sun, Shyamali Ghosh, Simon N. Stacey, Magali MouyJona Saemundsdottir, Valgerdur M. Backman, Kristleifur Kristjansson, Alejandro Tres, Alan W. Partin, Marjo T. Albers-Akkers, Javier Godino-Ivan Marcos, Patrick C. Walsh, Dorine W. Swinkels, Sebastian Navarrete, Sarah D. Isaacs, Katja K. Aben, Theresa Graif, John Cashy, Manuel Ruiz-Echarri, Kathleen E. Wiley, Brian K. Suarez, J. Alfred Witjes, Mike Frigge, Carole Ober, Eirikur Jonsson, Gudmundur V. Einarsson, Jose I. Mayordomo, Lambertus A. Kiemeney, William B. Isaacs, William J. Catalona, Rosa B. Barkardottir, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong*, Kari Stefansson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

737 Scopus citations

Abstract

Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (∼42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalNature Genetics
Volume39
Issue number5
DOIs
StatePublished - May 2007

Funding

We thank the patients and their family members whose contributions made this work possible. We also thank the nurses at Noatun (deCODE’s sample recruitment center), personnel at the deCODE core facilities and at the Department of Pathology at Landspitali University Hospital for their hard work and enthusiasm. We acknowledge M. Gielzak, G. Yan and J. Sauvageot (Johns Hopkins Hospital) for their assistance and W.T. Gerrard, M. Duhon, John and Jennifer Chalsty and D. Koch (also at Johns Hopkins Hospital) for their support. We also thank participants and clinicians at the Northwestern University, the University of Chicago, Johns Hopkins Hospital, the Radboud University Nijmegen Medical Centre and the Oncology Department of the Zaragoza Hospital. This project was funded in part by contract number 018827 (Polygene) from the 6th Framework Program of the European Union and by Department of Defense Congressionally Directed Medical Research Program grant W81XWH-05-1-0074.

ASJC Scopus subject areas

  • Genetics

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