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 × 10−8 to P = 2.7 × 10−33).
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Acknowledgements
These are detailed in the Supplementary Note.
Other members of The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, The UK ProtecT Study Collaborators and The PRACTICAL Consortium (membership lists provided in the Supplementary Note) collected clinical samples and provided data management.
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R.A.E. and D.F.E. designed the study, wrote the paper and are joint principal investigators (PIs) on the GWAS. R.A.E. is PI of the UKGPCS and project managed this study. Z.K.-J. coordinated the PRACTICAL genotyping and M.G. coordinated the administration. Z.K.-J., S.M.E., D.A.L., M.T., E.J.S. and C.S.C. coordinated sample collation, provided molecular advice and performed molecular work on UK samples. A.A.A.O. and D.F.E. performed the analyses; J.M. provided database and bioinformatic support for Illumina data. G.G.G., J.L.H. and D.R.E. are PIs of the Australian studies; M.C.S. led the Australian genotyping. G.S. coordinated the Australian studies. K.M. and R.A.E. are joint PIs of the PCRF study; A.L. and J.-F.L. coordinated sample collection. B.E.H. and C.A.H. lead the MEC consortium. J.S. is PI of the Tampere study; T.W. and T.L.T. coordinated sample collation, provided molecular advice and performed molecular work. F.C.H., D.E.N. and J.L.D. are joint PIs of ProtecT; S.J.L. helped with control matching for the UK. J.L.S. is PI of the Fred Hutchinson study, and E.A.O. is PI of the NHGRI genotyping for PROGRESS; L.M.F. and J.S.K. coordinated data collation. S.A.I. is PI of the USC study, E.M.J. is PI of the NC_CCPC study, S.N.T. and D.S. are PIs of the Mayo Clinic study and S.J.Mc. coordinated data collation. J.Y.P. is PI of the Moffit study, J.C. is PI of the Queensland study, A.S. led the Queensland genotyping, J.L.D. is PI of the Tasprac study, W.V. is PI of the Ulm study and C.M. led the genotyping. T.D. is PI of the Hannover study, T.R.R. is PI of the UPenn study, K.A.C. is PI of the FMHS study, L.C.A. is PI of the Utah study, P.O.C. and P.H. are PIs of the Valais study and W.D.F. led the molecular work. M.Z. is PI of the BiPAS study, R.K. is PI of the PCMUS study. G.C. is PI of the CHSH, H.-W.Z. led the genotyping and Y-J.L. provided study set up advice to the CHSH. A.T.A.-J., A.L.H., L.T.O., R.A.W., E.C.P., E.J.S., D.P.D., A.H., R.A.H., V.S.K., C.C.P., N.V.A., C.J.W., A.T., T.C., C.O., L.N.K., L.L.M., A.A., A.C., D.M.K., E.M.K., M.C.S., R.C., A.D.J., A.S., T.A.S., J.P.-S., S.C., J.A., R.A.G., J.B., M.A.K., F.L., A.P., B.P., J.S., A.M., M.L., K.L., A.M.R., E.M.L., J.F., H.K., C.S., K.S. and A.M. identified and collected clinical material, processed samples, undertook genotyping and collated data.
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Membership list provided in the Supplementary Note.
Full list of participants is provided in the Supplementary Note.
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Supplementary Figures 1 and 2, Supplementary Tables 1–13 and Supplementary Note (PDF 922 kb)
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Eeles, R., Kote-Jarai, Z., Al Olama, A. et al. Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. Nat Genet 41, 1116–1121 (2009). https://doi.org/10.1038/ng.450
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DOI: https://doi.org/10.1038/ng.450
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