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

568 Citations (Scopus)

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
Pages (from-to)977-983
Number of pages7
JournalNature Genetics
Volume39
Issue number8
DOIs
Publication statusPublished - Aug 2007

Bibliographical note

Funding Information:
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

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