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 Birgisdottir; Shyamali 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

doi:10.1038/ng2062

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

561 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 (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.

Original language	English
Journal	Nature Genetics
Volume	39
Issue number	8
Pages (from-to)	977-983
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng2062
Publication status	Published - 2007

Keywords

Case-Control Studies
Chromosomes, Human, Pair 17
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Haplotypes
Hepatocyte Nuclear Factor 1-beta
Humans
Male
Polymorphism, Single Nucleotide
Prostatic Neoplasms

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng2062

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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

Gudmundsson, J, Sulem, P, Steinthorsdottir, V, Bergthorsson, JT, Thorleifsson, G, Manolescu, A, Rafnar, T, Gudbjartsson, D, Agnarsson, BA, Baker, A, Sigurdsson, A, Benediktsdottir, KR, Jakobsdottir, M, Blondal, T, Stacey, SN, Helgason, A, Gunnarsdottir, S, Olafsdottir, A, Kristinsson, KT, Birgisdottir, B, Ghosh, S, Thorlacius, S, Magnusdottir, D, Stefansdottir, G, Kristjansson, K, Bagger, Y, Wilensky, RL, Reilly, MP, Morris, AD, Kimber, CH, Adeyemo, A, Chen, Y, Zhou, J, So, W-Y, Tong, PCY, Ng, MCY, Hansen, T, Andersen, G, Borch-Johnsen, K, Jorgensen, T, Tres, A, Fuertes, F, Ruiz-Echarri, M, Asin, L, Saez, B, van Boven, E, Klaver, S, Swinkels, DW, Aben, KK, Graif, T, Cashy, J, Suarez, BK, van Vierssen Trip, O, Frigge, ML, Ober, C, Hofker, MH, Wijmenga, C, Christiansen, C, Rader, DJ, Palmer, CNA, Rotimi, C, Chan, JCN, Pedersen, O, Sigurdsson, G, Benediktsson, R, Jonsson, E, Einarsson, GV, Mayordomo, JI, Catalona, WJ, Kiemeney, LA, Barkardottir, RB, Gulcher, JR, Thorsteinsdottir, U, Kong, A & Stefansson, K 2007, 'Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes', Nature Genetics, vol. 39, no. 8, pp. 977-983. https://doi.org/10.1038/ng2062

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

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 (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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AU - Gudmundsson, Julius

AU - Sulem, Patrick

AU - Steinthorsdottir, Valgerdur

AU - Bergthorsson, Jon T

AU - Thorleifsson, Gudmar

AU - Manolescu, Andrei

AU - Rafnar, Thorunn

AU - Gudbjartsson, Daniel

AU - Agnarsson, Bjarni A

AU - Baker, Adam

AU - Sigurdsson, Asgeir

AU - Benediktsdottir, Kristrun R

AU - Jakobsdottir, Margret

AU - Blondal, Thorarinn

AU - Stacey, Simon N

AU - Helgason, Agnar

AU - Gunnarsdottir, Steinunn

AU - Olafsdottir, Adalheidur

AU - Kristinsson, Kari T

AU - Birgisdottir, Birgitta

AU - Ghosh, Shyamali

AU - Thorlacius, Steinunn

AU - Magnusdottir, Dana

AU - Stefansdottir, Gerdur

AU - Kristjansson, Kristleifur

AU - Bagger, Yu

AU - Wilensky, Robert L

AU - Reilly, Muredach P

AU - Morris, Andrew D

AU - Kimber, Charlotte H

AU - Adeyemo, Adebowale

AU - Chen, Yuanxiu

AU - Zhou, Jie

AU - So, Wing-Yee

AU - Tong, Peter C Y

AU - Ng, Maggie C Y

AU - Hansen, Torben

AU - Andersen, Gitte

AU - Borch-Johnsen, Knut

AU - Jorgensen, Torben

AU - Tres, Alejandro

AU - Fuertes, Fernando

AU - Ruiz-Echarri, Manuel

AU - Asin, Laura

AU - Saez, Berta

AU - van Boven, Erica

AU - Klaver, Siem

AU - Swinkels, Dorine W

AU - Aben, Katja K

AU - Graif, Theresa

AU - Cashy, John

AU - Suarez, Brian K

AU - van Vierssen Trip, Onco

AU - Frigge, Michael L

AU - Ober, Carole

AU - Hofker, Marten H

AU - Wijmenga, Cisca

AU - Christiansen, Claus

AU - Rader, Daniel J

AU - Palmer, Colin N A

AU - Rotimi, Charles

AU - Chan, Juliana C N

AU - Pedersen, Oluf

AU - Sigurdsson, Gunnar

AU - Benediktsson, Rafn

AU - Jonsson, Eirikur

AU - Einarsson, Gudmundur V

AU - Mayordomo, Jose I

AU - Catalona, William J

AU - Kiemeney, Lambertus A

AU - Barkardottir, Rosa B

AU - Gulcher, Jeffrey R

AU - Thorsteinsdottir, Unnur

AU - Kong, Augustine

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AB - 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.

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 17

KW - Diabetes Mellitus, Type 2

KW - Genetic Predisposition to Disease

KW - Haplotypes

KW - Hepatocyte Nuclear Factor 1-beta

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Prostatic Neoplasms

U2 - 10.1038/ng2062

DO - 10.1038/ng2062

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C2 - 17603485

SN - 1061-4036

VL - 39

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JO - Nature: New biology

JF - Nature: New biology

IS - 8

ER -

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

Abstract

Keywords

UN SDGs

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