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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

561 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)977-983
Number of pages7
JournalNature Genetics
Volume39
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Genetics

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