全基因组关联研究在8q24区域鉴定出第二个前列腺癌易感变异位点。

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

作者信息

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

机构信息

deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

出版信息

Nat Genet. 2007 May;39(5):631-7. doi: 10.1038/ng1999. Epub 2007 Apr 1.

DOI:10.1038/ng1999

PMID:17401366

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.

摘要

前列腺癌是发达地区男性中最常见的非皮肤癌，非裔美国男性的发病率和死亡率在全球位居前列。我们在此报告8q24区域的第二个基因变异，该变异与我们最近发现的另一个变异共同作用，在欧洲裔个体中约占前列腺癌病例的11% - 13%，在非裔美国人中占31%。我们通过使用Illumina HumanHap300 BeadChip对1453名冰岛前列腺癌患者和3064名对照进行全基因组关联扫描，随后进行四项重复研究，从而有了当前这一发现。该发现中的一个关键步骤是构建了一个14个单核苷酸多态性（SNP）的单倍型，它能有效标记欧洲裔个体中一种相对罕见（2% - 4%）的易感变异，而这种变异在非裔美国人中却非常常见（约42%）。新发现的变异与诊断年龄较早的患者有更强的关联性。