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

Julius Gudmundsson, Patrick Sulem, Valgerdur Steinthorsdottir, Jon T. Bergthorsson, Gudmar Thorleifsson, Andrei Manolescu, Thorunn Rafnar, Daniel Gudbjartsson, Bjarni A. Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R. Benediktsdottir, Margret Jakobsdottir, Thorarinn Blondal, Simon N. Stacey, Agnar Helgason, Steinunn Gunnarsdottir, Adalheidur Olafsdottir, Kari T. Kristinsson, Birgitta BirgisdottirShyamali Ghosh, Steinunn Thorlacius, Dana Magnusdottir, Gerdur Stefansdottir, Kristleifur Kristjansson, Yu Bagger, Robert L. Wilensky, Muredach P. Reilly, Andrew D. Morris, Charlotte H. Kimber, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Wing-Yee So, Peter C. Y. Tong, Maggie C. Y. Ng, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Alejandro Tres, Fernando Fuertes, Manuel Ruiz-Echarri, Laura Asin, Berta Saez, Erica van Boven, Siem Klaver, Dorine W. Swinkels, Katja K. Aben, Theresa Graif, John Cashy, Brian K. Suarez, Onco van Vierssen Trip, Michael L. Frigge, Carole Ober, Marten H. Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J. Rader, Colin N. A. Palmer, Charles Rotimi, Juliana C. N. Chan, Oluf Pedersen, Gunnar Sigurdsson, Rafn Benediktsson, Eirikur Jonsson, Gudmundur V. Einarsson, Jose I. Mayordomo, William J. Catalona, Lambertus A. Kiemeney, Rosa B. Barkardottir, Jeffrey R. Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson

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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 (HNF1ß), 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.
    Original languageEnglish
    Pages (from-to)977-983
    Number of pages7
    JournalNature Genetics
    Volume39
    Issue number8
    DOIs
    Publication statusPublished - 2007

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    Gudmundsson, J., Sulem, P., Steinthorsdottir, V., Bergthorsson, J. T., Thorleifsson, G., Manolescu, A., Rafnar, T., Gudbjartsson, D., Agnarsson, B. A., Baker, A., Sigurdsson, A., Benediktsdottir, K. R., Jakobsdottir, M., Blondal, T., Stacey, S. N., Helgason, A., Gunnarsdottir, S., Olafsdottir, A., Kristinsson, K. T., ... Stefansson, K. (2007). Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nature Genetics, 39(8), 977-983. https://doi.org/10.1038/ng2062