Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 (original) (raw)

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Acknowledgements

We thank the patients and their family members whose contributions made this work possible. We also thank the nurses at Noatun (deCODE's sample recruitment center), personnel at the deCODE core facilities and at the Department of Pathology at Landspitali University Hospital for their hard work and enthusiasm. We acknowledge M. Gielzak, G. Yan and J. Sauvageot (Johns Hopkins Hospital) for their assistance and W.T. Gerrard, M. Duhon, John and Jennifer Chalsty and D. Koch (also at Johns Hopkins Hospital) for their support. We also thank participants and clinicians at the Northwestern University, the University of Chicago, Johns Hopkins Hospital, the Radboud University Nijmegen Medical Centre and the Oncology Department of the Zaragoza Hospital. This project was funded in part by contract number 018827 (Polygene) from the 6th Framework Program of the European Union and by Department of Defense Congressionally Directed Medical Research Program grant W81XWH-05-1-0074.

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Author notes

1. Julius Gudmundsson, Patrick Sulem, Andrei Manolescu and Laufey T Amundadottir: These authors contributed equally to this work.

Authors and Affiliations

1. deCODE genetics, Sturlugata 8, Reykjavik, 101, Iceland
   Julius Gudmundsson, Patrick Sulem, Andrei Manolescu, Laufey T Amundadottir, Daniel Gudbjartsson, Agnar Helgason, Thorunn Rafnar, Jon T Bergthorsson, Adam Baker, Asgeir Sigurdsson, Margret Jakobsdottir, Thorarinn Blondal, Jelena Kostic, Shyamali Ghosh, Simon N Stacey, Magali Mouy, Jona Saemundsdottir, Valgerdur M Backman, Kristleifur Kristjansson, Mike Frigge, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson
2. Department of Pathology, Landspitali-University Hospital, Reykjavik, 101, Iceland
   Bjarni A Agnarsson, Kristrun R Benediktsdottir & Rosa B Barkardottir
3. Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, 27157, North Carolina, USA
   Jianfeng Xu & Jielin Sun
4. Division of Medical Oncology, Lozano Blesa University Hospital, University of Zaragoza, Zaragoza, 50009, Spain
   Alejandro Tres, Manuel Ruiz-Echarri & Jose I Mayordomo
5. Department of Urology, Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, 21209, Maryland, USA
   Alan W Partin, Patrick C Walsh, Sarah D Isaacs, Kathleen E Wiley & William B Isaacs
6. Thrombosis Service, GM Nijmegen, 6503, The Netherlands
   Marjo T Albers-Akkers
7. The Institute of Health Sciences, Nanotechnology Institute of Aragon, Zaragoza, 50009, Spain
   Javier Godino-Ivan Marcos
8. Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
   Dorine W Swinkels
9. Division of Radiation Oncology, University Hospital, Zaragoza, Spain
   Sebastian Navarrete
10. Comprehensive Cancer Center East, BG Nijmegen, 6501, The Netherlands
    Katja K Aben
11. Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, HB Nijmegen, 6500, The Netherlands
    Katja K Aben
12. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
    Theresa Graif, John Cashy & William J Catalona
13. Department of Psychiatry, Washington University School of Medicine, St. Louis, 63110, Missouri, USA
    Brian K Suarez
14. Department of Urology, Radboud University Nijmegen Medical Center, HB Nijmegen, 6500, The Netherlands
    J Alfred Witjes & Lambertus A Kiemeney
15. Department of Human Genetics, University of Chicago, Chicago, 60637, Illinois, USA
    Carole Ober
16. Department of Urology, Landspitali-University Hospital, Reykjavik, 101, Iceland
    Eirikur Jonsson & Gudmundur V Einarsson
17. Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, HB Nijmegen, 6500, The Netherlands
    Lambertus A Kiemeney

Authors

1. Julius Gudmundsson
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2. Patrick Sulem
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3. Andrei Manolescu
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4. Laufey T Amundadottir
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5. Daniel Gudbjartsson
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6. Agnar Helgason
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7. Thorunn Rafnar
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8. Adam Baker
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9. Asgeir Sigurdsson
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10. Kristrun R Benediktsdottir
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11. Margret Jakobsdottir
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12. Jianfeng Xu
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13. Thorarinn Blondal
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14. Jelena Kostic
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15. Jielin Sun
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16. Shyamali Ghosh
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17. Simon N Stacey
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18. Magali Mouy
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19. Jona Saemundsdottir
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20. Valgerdur M Backman
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21. Kristleifur Kristjansson
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22. Alejandro Tres
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23. Alan W Partin
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24. Marjo T Albers-Akkers
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25. Javier Godino-Ivan Marcos
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26. Patrick C Walsh
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27. Dorine W Swinkels
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28. Sebastian Navarrete
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29. Sarah D Isaacs
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30. Katja K Aben
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31. Theresa Graif
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32. John Cashy
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33. Manuel Ruiz-Echarri
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34. Kathleen E Wiley
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35. Brian K Suarez
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36. J Alfred Witjes
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37. Mike Frigge
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38. Carole Ober
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39. Eirikur Jonsson
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40. Jose I Mayordomo
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41. Lambertus A Kiemeney
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42. William B Isaacs
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43. William J Catalona
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44. Rosa B Barkardottir
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45. Jeffrey R Gulcher
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46. Unnur Thorsteinsdottir
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47. Augustine Kong
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48. Kari Stefansson
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Contributions

The principal investigators of the replication sample sets are J.I.M., L.A.K., W.B.I. and W.J.C.

Corresponding authors

Correspondence toAugustine Kong or Kari Stefansson.

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Competing interests

J.G., P.S., A.M., L.T.A., D.G., A.H., T.R., J.T.B., A.B., A.S., M.J., T.B., J.K., S.G., S.N.S., M.M., J. Saemundsdottir, V.M.B., K.K., M.F., J.R.G., U.T., A.K. and K.S. are employees of and shareholders in deCODE genetics.

Supplementary information

Supplementary Fig. 1

Estimates of relative risk for haplotypes defined by rs16901979 and rs1447295. (PDF 17 kb)

Supplementary Fig. 2

A Q-Q plot of the 316,515 chi-square statistics from the single point association. (PDF 46 kb)

Supplementary Table 1

Block-haplotypes with estimated frequency 1% or higher in the two LD blocks containing rs1447295 and HapC/rs16901979. (PDF 29 kb)

Supplementary Table 2

Age at diagnosis for prostate cancer in Iceland, Spain, the Netherlands and the US. (PDF 15 kb)

Supplementary Table 3

Distribution of observed and expected association results, by chromosome and significance level, for the 316,515 SNPs used in the genome-wide association analysis of the Icelandic prostate cancer cases and controls. (PDF 17 kb)

Supplementary Table 4

Information about primers and assays. (PDF 20 kb)

Supplementary Methods (PDF 61 kb)

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Gudmundsson, J., Sulem, P., Manolescu, A. et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.Nat Genet 39, 631–637 (2007). https://doi.org/10.1038/ng1999

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• Received: 06 December 2006
• Accepted: 16 February 2007
• Published: 01 April 2007
• Issue Date: May 2007
• DOI: https://doi.org/10.1038/ng1999