Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility

• Published in: Nature genetics Vol. 41; no. 10; pp. 1122 - 1126
• Main Authors: Sigurdsson, Asgeir, Smith, Jeffrey R, Jakobsdottir, Margret, Thorsteinsdottir, Unnur, Magnusdottir, Droplaug N, Benediktsdottir, Kristrun R, McReynolds, Kate M, Frigge, Michael L, Jonsson, Eirikur, Navarrete, Sebastian, Kiemeney, Lambertus A, Wahlfors, Tiina, Helfand, Brian T, Barkardottir, Rosa B, Breyer, Joan P, Aben, Katja K, Suarez, Brian K, Saez, Berta, Agnarsson, Bjarni A, Murillo, Laura, Tammela, Teuvo, Stacey, Simon N, Bradley, Kevin M, Einarsson, Gudmundur V, Schleutker, Johanna, Gudmundsson, Julius, Zanon, Carlo, Gudbjartsson, Daniel F, Godino, Javier, Orlygsdottir, Gudbjorg, Rafnar, Thorunn, Gylfason, Arnaldur, Kan, Donghui, Blondal, Thorarinn, Kong, Augustine, Kristjansson, Kristleifur, Polo, Eduardo, van Oort, Inge M, Stefansson, Kari, Fuertes, Fernando, Catalona, William J, Gulcher, Jeffrey R, Sulem, Patrick, Mayordomo, Jose I
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Colorectal cancer; Disease Susceptibility; DNA - genetics; DNA Replication; Estimates; European Continental Ancestry Group - genetics; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic markers; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genome-Wide Association Study; Health aspects; Health risks; Human Genetics; Humans; Iceland; letter; Male; Medical sciences; Molecular and cellular biology; Molecular genetics; Nephrology. Urinary tract diseases; Polymorphism, Single Nucleotide; Prevention; Prostate cancer; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - genetics; Replication; Risk Factors; Single nucleotide polymorphisms; Studies; Tumors of the urinary system; Urinary tract. Prostate gland; Iceland; United States; Variant; Urinary system disease; Prostate disease; Replication; Identification; Malignant tumor; Male genital diseases; Prostate cancer; Cancer
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.448

Julius Gudmundsson and colleagues report a prostate cancer genome-wide association follow-on study. They report variants at 3q21.3, 8q24.21 and 19q13.2 newly associated to prostate cancer susceptibility and the fine-mapping of the association signal at 11q13. We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 × 10 −10 ) on 3q21.3; two moderately correlated ( r 2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 × 10 −15 ) and rs445114[T] (OR = 1.14, P = 4.7 × 10 −10 ), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 × 10 −11 ) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 × 10 −12 ). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.