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Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array


Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10−8). More than 70 prostate cancer susceptibility loci, explaining 30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.

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Figure 1: Composition of the prostate part of the iCOGS chip.
Figure 2: Manhattan plot of associations for new iCOGS loci.
Figure 3: Regional association plots.


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Acknowledgments are detailed in the Supplementary Note.

Author information





R.A.E. and D.F.E. designed the study. R.A.E. is principal investigator of PRACTICAL. D.F.E. is Scientific Director of the COGS initiative. Z.K.-J. is co-investigator of PRACTICAL. R.A.E., D.F.E., Z.K.-J. and A.A.A.O. wrote the manuscript; the following named coauthors commented on the manuscript. A.A.A.O. and D.F.E. performed the statistical analyses; S.B. collated the data set. J.D. managed the database. Z.K.-J., E.J. Saunders, D.A.L. and M.T. coordinated sample collation and quality control for iCOGS PRACTICAL genotyping. S.J.-L. carried out pathway analysis and constructed regional plots, and T. Dadaev, K.G., M. Guy, R.A.W., E.J. Sawyer and A.M. managed the UKGPCS database and manifests for genotyping. C.L., A.M.D., C.B., D. Conroy, M.J.M., S.A., E.D., A. Lee, D.C.T., F.B. and D.V. carried out iCOGS PRACTICAL genotyping and set quality control standards. M. Ghoussaini selected the iCOGS PRACTICAL SNPs for fine-scale mapping. K.M. and A. Lophatananon collected some of the UKGPCS samples and controls. F.C.H., D.E.N. and J.L.D. are joint principal investigators of ProtecT. B.E.H. and L.L.M. are principal investigators of MEC; C.A.H. and F.S. are co-investigators. S.I.B. and D.A. are principal investigators of the PLCO study; G.A. is the principal investigator for the St. Louis screening center for PLCO; and S.J.C. and M.Y. led the genotyping for PLCO. S.G., R.B.H. and W.R.D. provided samples for PLCO. D.J.H. directs and P. Kraft coordinates data collection and management/analysis for HPFS. M.W. is the principal investigator of CPCS1 and CPCS2. B.G.N., S.F.N. S.E.B., P. Klarskov and M.A.R. have collected samples and data, and contributed to genotyping in this study. J.L.S. is principal investigator of the Fred Hutchinson–based study; E.A.O. collaborated on the study; L.M.F. and S.K. coordinated data collation; and E.M.K. and D.M.K. coordinated the preparation of samples. L.C.-A. is principal investigator of the Utah study; C.T. is the analyst; and R.A.S. is the surgeon. S.L. is a co-investigator of the BPC3 Consortium. H.G. is principal investigator of the CAPS and STHM1 study; J.A., M.A., F.W., S.L.Z. and J.X. have contributed to sample collection, clinical data retrieval, analyses and molecular work. S.A.I. is principal investigator of the USC study, and E.M.J. is principal investigator of SFPCS; M.C. Stem and R.C. led the genotyping of both studies. A.D.J. and A. Shahabi were both involved in genotype data production for the USC and SFPCS studies. A.S.K. is principal investigator of WUGS. B.D. and G.C. collected and collated clinical data and performed sample selection. M.R.T. is the principal investigator of the IPO-Porto study; S.M. and P.P. collected familial and molecular data on cases. L.B.S. and W.J.B. are the principal investigators of SCCS; L.B.S., W.J.B., W.Z. and Q.C. were responsible for the original collection of the samples. W.Z. and Q.C. coordinated sample retrieval, DNA extraction and genotyping. L.B.S. oversaw the assembly of the phenotype data. J.B. and J.A.C. are principal investigators of the Queensland study with input from A.B.S., F.L. and S.S. coordinated the data collation. K.A.C. and E.L. provided imputed data for genotyping in carriers of the mutation encoding the p.Gly84Glu alteration in the HOXB13 region. G.G.G., J.L.H., D.R.E. and G.S. are principal investigators of the Australian studies; M.C. Southey manages the molecular work. J.S. is principal investigator of the Tampere study; T.W. collected and collated clinical data and performed sample selection. T.L.J.T. coordinated sample collection. H.B. is principal investigator of the ESTHER study; D.R. and C.S. contributed to design and data collection; and H.M. is study coordinator. J.Y.P. is principal investigator of the Moffitt study; T.A.S. and H.-Y.L. are contributors to this study. R. Kaneva is principal investigator of the PCMUS study; C.S. provided the samples in the PCMUS study; V.M. oversaw the data collation. C.C. and J.L. are principal investigators of the Poland study; C.C. and D.W. collated the samples. C.M. and W.V. are principal investigators of the Ulm study; A.E.R. identified and collected clinical material, processed samples, undertook genotyping and/or collated data. E.R. is principal investigator of EPIC; F.C., R. Kaaks and D. Campa are investigators in Germany. T.J.K. is principal investigator of the EPIC-Oxford cohort and collected clinical material. R.C.T. collated data. K.-T.K. is principal investigator of the EPIC-Norfolk study. S.N.T. and D.S. are principal investigators of the Mayo Clinic study; S.K.M. coordinated data collation. M.M.G. provided samples for the ACS study. P.D.P.P. and N.P. provided samples for the East Anglia SEARCH study. C.S.C. gave advice about results and contributed to the manuscript. A.C.A. undertook risk prediction analysis for clinical application. D.P.D., A.H., R.A.H., V.S.K., C.C.P., N.J.V.A., C.J.W., A.T., T. Dudderidge, C.O., A.A., A.C., J.V. and A. Siddiq identified and collected clinical material. 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, assisted in genotyping and provided data management. Members of the COGS–Cancer Research UK GWAS–ELLIPSE (part of GAME-ON) Initiatives, the Australian Prostate Cancer Bioresource, the UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology, the UK ProtecT Study Collaborators, the PRACTICAL Consortium and CSC collected clinical samples and/or assisted in genotyping and/or provided data management and/or discussion of the data.

Corresponding author

Correspondence to Rosalind A Eeles.

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The authors declare no competing financial interests.

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A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

Supplementary information

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Supplementary Tables 1–8, Supplementary Figures 1–4 and Supplementary Note (PDF 12601 kb)

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Eeles, R., Olama, A., Benlloch, S. et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet 45, 385–391 (2013).

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