Multiple newly identified loci associated with prostate cancer susceptibility.
Eeles RA., Kote-Jarai Z., Giles GG., Olama AAA., Guy M., Jugurnauth SK., Mulholland S., Leongamornlert DA., Edwards SM., Morrison J., Field HI., Southey MC., Severi G., Donovan JL., Hamdy FC., Dearnaley DP., Muir KR., Smith C., Bagnato M., Ardern-Jones AT., Hall AL., O'Brien LT., Gehr-Swain BN., Wilkinson RA., Cox A., Lewis S., Brown PM., Jhavar SG., Tymrakiewicz M., Lophatananon A., Bryant SL., UK Genetic Prostate Cancer Study Collaborators None., British Association of Urological Surgeons' Section of Oncology None., UK ProtecT Study Collaborators None., Horwich A., Huddart RA., Khoo VS., Parker CC., Woodhouse CJ., Thompson A., Christmas T., Ogden C., Fisher C., Jamieson C., Cooper CS., English DR., Hopper JL., Neal DE., Easton DF.
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 x 10(-8) to P = 8.7 x 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.