Multiple newly identified loci associated with prostate cancer susceptibility

Rosalind A. Eeles, Zsofia Kote-Jarai, Graham G. Giles, Ali Amin Al Olama, Michelle Guy, Sarah K. Jugurnauth, Shani Mulholland, Daniel A. Leongamornlert, Stephen M. Edwards, Jonathan Morrison, Helen I. Field, Melissa C. Southey, Gianluca Severi, Jenny L. Donovan, Freddie C. Hamdy, David P. Dearnaley, Kenneth R. Muir, Charmaine Smith, Melisa Bagnato, Audrey T. Ardern-JonesAmanda L. Hall, Lynne T. O'Brien, Beatrice N. Gehr-Swain, Rosemary A. Wilkinson, Angie Cox, Sarah Lewis, Paul M. Brown, Sameer G. Jhavar, Malgorzata Tymrakiewicz, Artitaya Lophatananon, Sarah L. Bryant, Alan Horwich, Robert A. Huddart, Vincent S. Khoo, Christopher C. Parker, Christopher J. Woodhouse, Alan Thompson, Tim Christmas, Chris Ogden, Cyril Fisher, Charles Jamieson, Colin S. Cooper, Dallas R. English, John L. Hopper, David E. Neal, Douglas F. Easton

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676 Citations (Scopus)

Abstract

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at ≤60 years or with a family history of disease, and 1,894 population-screened controls with a low prostate-specific antigen (PSA) concentration (<0.5 ng/ml). We analyzed these samples for 541,129 SNPs using the Illumina Infinium platform. Initial putative associations were confirmed using a further 3,268 cases and 3,366 controls. We identified seven loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 × 10-8 to P = 8.7 × 10-29). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3.

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalNature Genetics
Volume40
Issue number3
DOIs
Publication statusPublished - 1 Mar 2008
Externally publishedYes

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