Mitra, AV.,
Bancroft, EK.,
Barbachano, Y.,
Page, EC.,
Foster, CS.,
Jameson, C.,
Mitchell, G.,
Lindeman, GJ.,
Stapleton, A.,
Suthers, G.,
et al.
(2011)
Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int, Vol.107(1),
pp.28-39,
Show Abstract
To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported.
Kote-Jarai, Z.,
Olama, AA.,
Giles, GG.,
Severi, G.,
Schleutker, J.,
Weischer, M.,
Campa, D.,
Riboli, E.,
Key, T.,
Gronberg, H.,
et al.
(2011)
Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. Nat Genet, Vol.43(8),
pp.785-791,
Show Abstract
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ∼25% of the familial risk in this disease, have now been identified.
Edwards, SM.,
Evans, DG.,
Hope, Q.,
Norman, AR.,
Barbachano, Y.,
Bullock, S.,
Kote-Jarai, Z.,
Meitz, J.,
Falconer, A.,
Osin, P.,
et al.
(2010)
Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. Br J Cancer, Vol.103(6),
pp.918-924,
Show Abstract
The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours.
Al Olama, AA.,
Kote-Jarai, Z.,
Giles, GG.,
Guy, M.,
Morrison, J.,
Severi, G.,
Leongamornlert, DA.,
Tymrakiewicz, M.,
Jhavar, S.,
Saunders, E.,
et al.
(2009)
Multiple loci on 8q24 associated with prostate cancer susceptibility. Nat Genet, Vol.41(10),
pp.1058-1060,
Show Abstract
Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.
Eeles, RA.,
Kote-Jarai, Z.,
Al Olama, AA.,
Giles, GG.,
Guy, M.,
Severi, G.,
Muir, K.,
Hopper, JL.,
Henderson, BE.,
Haiman, CA.,
et al.
(2009)
Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet, Vol.41(10),
pp.1116-1121,
Show Abstract
Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).
Eeles, RA.,
Kote-Jarai, Z.,
Giles, GG.,
Olama, AA.,
Guy, M.,
Jugurnauth, SK.,
Mulholland, S.,
Leongamornlert, DA.,
Edwards, SM.,
Morrison, J.,
et al.
(2008)
Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet, Vol.40(3),
pp.316-321,
Show 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 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.
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