Letter abstract


Nature Genetics 39, 977 - 983 (2007)
Published online: 1 July 2007 | doi:10.1038/ng2062

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

Julius Gudmundsson1,30, Patrick Sulem1,30, Valgerdur Steinthorsdottir1, Jon T Bergthorsson1, Gudmar Thorleifsson1, Andrei Manolescu1, Thorunn Rafnar1, Daniel Gudbjartsson1, Bjarni A Agnarsson2, Adam Baker1, Asgeir Sigurdsson1, Kristrun R Benediktsdottir2, Margret Jakobsdottir1, Thorarinn Blondal1, Simon N Stacey1, Agnar Helgason1, Steinunn Gunnarsdottir1, Adalheidur Olafsdottir1, Kari T Kristinsson1, Birgitta Birgisdottir1, Shyamali Ghosh1, Steinunn Thorlacius1, Dana Magnusdottir1, Gerdur Stefansdottir1, Kristleifur Kristjansson1, Yu Bagger3, Robert L Wilensky4, Muredach P Reilly4, Andrew D Morris5, Charlotte H Kimber6, Adebowale Adeyemo7, Yuanxiu Chen7, Jie Zhou7, Wing-Yee So8, Peter C Y Tong8, Maggie C Y Ng8, Torben Hansen9, Gitte Andersen9, Knut Borch-Johnsen9,10,11, Torben Jorgensen11, Alejandro Tres12,13, Fernando Fuertes14, Manuel Ruiz-Echarri12, Laura Asin13, Berta Saez13, Erica van Boven15, Siem Klaver16, Dorine W Swinkels16, Katja K Aben17, Theresa Graif18, John Cashy18, Brian K Suarez19, Onco van Vierssen Trip20, Michael L Frigge1, Carole Ober21, Marten H Hofker22,23, Cisca Wijmenga24,25, Claus Christiansen3, Daniel J Rader4, Colin N A Palmer6, Charles Rotimi7, Juliana C N Chan8, Oluf Pedersen9,10, Gunnar Sigurdsson26,27, Rafn Benediktsson26,27, Eirikur Jonsson28, Gudmundur V Einarsson28, Jose I Mayordomo12,13, William J Catalona18, Lambertus A Kiemeney29, Rosa B Barkardottir2, Jeffrey R Gulcher1, Unnur Thorsteinsdottir1, Augustine Kong1 & Kari Stefansson1

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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 (HNF1beta), 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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  1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
  2. Department of Pathology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
  3. Center for Clinical and Basic Research A/S, DK-2750 Ballerup, Denmark.
  4. University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  5. Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.
  6. Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.
  7. National Human Genome Center, Howard University, Department of Community and Family Medicine, Washington, DC 20060, USA.
  8. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong.
  9. Steno Diabetes Center, DK-2820 Copenhagen, Denmark.
  10. Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.
  11. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
  12. Division of Medical Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.
  13. The Institute of Health Sciences, Nanotechnology Institute of Aragon, 50009 Zaragoza, Spain.
  14. Division of Radiation Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.
  15. Department of Urology, Maas Ziekenhuis, 5830 AB Boxmeer, The Netherlands.
  16. Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
  17. Comprehensive Cancer Center East, 6501 BG Nijmegen, and Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
  18. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
  19. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
  20. Department of Urology, Gelderse Vallei Hospital, 6716 RP Ede, The Netherlands.
  21. Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
  22. Department of Pathology and Laboratory Medicine, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
  23. Department of Molecular Genetics, Maastricht University, 6200 MD Maastricht, The Netherlands.
  24. Department of Genetics, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
  25. Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands.
  26. Landspitali-University Hospital, 101 Reykjavik, Iceland.
  27. Icelandic Heart Association, 201 Kopavogur, Iceland.
  28. Department of Urology, Landspitali-University Hospital, 101 Reykjavik, Iceland.
  29. Department of Epidemiology and Biostatistics and Department of Urology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
  30. These authors contributed equally to this work.

Correspondence to: Kari Stefansson1 e-mail: kstefans@decode.is

Correspondence to: Julius Gudmundsson1,30 e-mail: julius.gudmundsson@decode.is



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