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Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. 2007
Julius Gudmundsson, and
Patrick Sulem, and
Andrei Manolescu, and
Laufey T Amundadottir, and
Daniel Gudbjartsson, and
Agnar Helgason, and
Thorunn Rafnar, and
Jon T Bergthorsson, and
Bjarni A Agnarsson, and
Adam Baker, and
Asgeir Sigurdsson, and
Kristrun R Benediktsdottir, and
Margret Jakobsdottir, and
Jianfeng Xu, and
Thorarinn Blondal, and
Jelena Kostic, and
Jielin Sun, and
Shyamali Ghosh, and
Simon N Stacey, and
Magali Mouy, and
Jona Saemundsdottir, and
Valgerdur M Backman, and
Kristleifur Kristjansson, and
Alejandro Tres, and
Alan W Partin, and
Marjo T Albers-Akkers, and
Javier Godino-Ivan Marcos, and
Patrick C Walsh, and
Dorine W Swinkels, and
Sebastian Navarrete, and
Sarah D Isaacs, and
Katja K Aben, and
Theresa Graif, and
John Cashy, and
Manuel Ruiz-Echarri, and
Kathleen E Wiley, and
Brian K Suarez, and
J Alfred Witjes, and
Mike Frigge, and
Carole Ober, and
Eirikur Jonsson, and
Gudmundur V Einarsson, and
Jose I Mayordomo, and
Lambertus A Kiemeney, and
William B Isaacs, and
William J Catalona, and
Rosa B Barkardottir, and
Jeffrey R Gulcher, and
Unnur Thorsteinsdottir, and
Augustine Kong, and
Kari Stefansson
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
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 (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.
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