Letter | Published:

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

Nature Genetics 39, 977–983 (2007) | Download Citation

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Abstract

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1β), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

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Acknowledgements

We thank the research subjects whose contribution made this work possible. We also thank the nurses at Noatun (deCODE's sample recruitment center) and personnel at the deCODE core facilities. This project was funded in part by contract number 018827 (Polygene) from the 6th Framework Program of the European Union and by US Department of Defense Congressionally Directed Medical Research Program W81XWH-05-1-0074. Support for the Africa America Diabetes Mellitus (AADM) study is provided by multiple institutes of the US National Institutes of Health: the National Center on Minority Health and Health Disparities (3T37TW00041-03S2), National Institute of Diabetes and Digestive and Kidney (DK072128), the National Human Genome Research Institute and the National Center for Research Resources (RR03048). The Scottish Diabetes case control study was funded by the Wellcome Trust. C.N.A.P. and A.M. are supported by the Scottish Executive Generation Scotland Initiative. The Hong Kong Diabetes case control study was supported by the Hong Kong Research Grants Committee Central Allocation Scheme CUHK 1/04C.

Author information

    • Julius Gudmundsson
    •  & Patrick Sulem

    These authors contributed equally to this work.

Affiliations

  1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

    • Julius Gudmundsson
    • , Patrick Sulem
    • , Valgerdur Steinthorsdottir
    • , Jon T Bergthorsson
    • , Gudmar Thorleifsson
    • , Andrei Manolescu
    • , Thorunn Rafnar
    • , Daniel Gudbjartsson
    • , Adam Baker
    • , Asgeir Sigurdsson
    • , Margret Jakobsdottir
    • , Thorarinn Blondal
    • , Simon N Stacey
    • , Agnar Helgason
    • , Steinunn Gunnarsdottir
    • , Adalheidur Olafsdottir
    • , Kari T Kristinsson
    • , Birgitta Birgisdottir
    • , Shyamali Ghosh
    • , Steinunn Thorlacius
    • , Dana Magnusdottir
    • , Gerdur Stefansdottir
    • , Kristleifur Kristjansson
    • , Michael L Frigge
    • , Jeffrey R Gulcher
    • , Unnur Thorsteinsdottir
    • , Augustine Kong
    •  & Kari Stefansson

  2. Department of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland.

    • Bjarni A Agnarsson
    • , Kristrun R Benediktsdottir
    •  & Rosa B Barkardottir

  3. Center for Clinical and Basic Research A/S, DK-2750 Ballerup, Denmark.

    • Yu Bagger
    •  & Claus Christiansen

  4. University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

    • Robert L Wilensky
    • , Muredach P Reilly
    •  & Daniel J Rader

  5. Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.

    • Andrew D Morris

  6. Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.

    • Charlotte H Kimber
    •  & Colin N A Palmer

  7. National Human Genome Center, Howard University, Department of Community and Family Medicine, Washington, DC 20060, USA.

    • Adebowale Adeyemo
    • , Yuanxiu Chen
    • , Jie Zhou
    •  & Charles Rotimi

  8. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.

    • Wing-Yee So
    • , Peter C Y Tong
    • , Maggie C Y Ng
    •  & Juliana C N Chan

  9. Steno Diabetes Center, DK-2820 Copenhagen, Denmark.

    • Torben Hansen
    • , Gitte Andersen
    • , Knut Borch-Johnsen
    •  & Oluf Pedersen

  10. Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.

    • Knut Borch-Johnsen
    •  & Oluf Pedersen

  11. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.

    • Knut Borch-Johnsen
    •  & Torben Jorgensen

  12. Division of Medical Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.

    • Alejandro Tres
    • , Manuel Ruiz-Echarri
    •  & Jose I Mayordomo

  13. The Institute of Health Sciences, Nanotechnology Institute of Aragon, 50009 Zaragoza, Spain.

    • Alejandro Tres
    • , Laura Asin
    • , Berta Saez
    •  & Jose I Mayordomo

  14. Division of Radiation Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.

    • Fernando Fuertes

  15. Department of Urology, Maas Ziekenhuis, 5830 AB Boxmeer, The Netherlands.

    • Erica van Boven

  16. Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.

    • Siem Klaver
    •  & Dorine W Swinkels

  17. Comprehensive Cancer Center East, 6501 BG Nijmegen, and Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.

    • Katja K Aben

  18. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

    • Theresa Graif
    • , John Cashy
    •  & William J Catalona

  19. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    • Brian K Suarez

  20. Department of Urology, Gelderse Vallei Hospital, 6716 RP Ede, The Netherlands.

    • Onco van Vierssen Trip

  21. Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.

    • Carole Ober

  22. Department of Pathology and Laboratory Medicine, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Marten H Hofker

  23. Department of Molecular Genetics, Maastricht University, 6200 MD Maastricht, The Netherlands.

    • Marten H Hofker

  24. Department of Genetics, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Cisca Wijmenga

  25. Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands.

    • Cisca Wijmenga

  26. Landspitali-University Hospital, 101 Reykjavik, Iceland.

    • Gunnar Sigurdsson
    •  & Rafn Benediktsson

  27. Icelandic Heart Association, 201 Kopavogur, Iceland.

    • Gunnar Sigurdsson
    •  & Rafn Benediktsson

  28. Department of Urology, Landspitali-University Hospital, 101 Reykjavik, Iceland.

    • Eirikur Jonsson
    •  & Gudmundur V Einarsson

  29. Department of Epidemiology and Biostatistics and Department of Urology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.

    • Lambertus A Kiemeney

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Competing interests

J.G., P.S., V.S., J.T.B., G.T., A.M., T.R., D.G., A.B., A.S., M.J., T.B., S.N.S., A.H., S. Gunnarsdottir, A.O., K.T.K., B.B., S. Ghosh, S.T., D.M., G.S., K.K., M.L.F., J.R.G., U.T., A.K. and K.S. are shareholders in deCODE genetics, Inc.

Corresponding authors

Correspondence to Julius Gudmundsson or Kari Stefansson.

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DOI

https://doi.org/10.1038/ng2062

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