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

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 (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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