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

被引：547

作者：

Gudmundsson, Julius

Sulem, Patrick

Steinthorsdottir, Valgerdur

Bergthorsson, Jon T.

Thorleifsson, Gudmar

Manolescu, Andrei

Rafnar, Thorunn

Gudbjartsson, Daniel

Agnarsson, Bjarni A.

Baker, Adam

Sigurdsson, Asgeir

Benediktsdottir, Kristrun R.

Jakobsdottir, Margret

Blondal, Thorarinn

Stacey, Simon N.

Helgason, Agnar

Gunnarsdottir, Steinunn

Olafsdottir, Adalheidur

Kristinsson, Kari T.

Birgisdottir, Birgitta

Ghosh, Shyamali

Thorlacius, Steinunn

Magnusdottir, Dana

Stefansdottir, Gerdur

Kristjansson, Kristleifur

Bagger, Yu

Wilensky, Robert L.

Reilly, Muredach P.

Morris, Andrew D.

Kimber, Charlotte H.

Adeyemo, Adebowale

Chen, Yuanxiu

Zhou, Jie

So, Wing-Yee

Tong, Peter C. Y.

Ng, Maggie C. Y.

Hansen, Torben

Andersen, Gitte

Borch-Johnsen, Knut

Jorgensen, Torben

Tres, Alejandro

Fuertes, Fernando

Ruiz-Echarri, Manuel

Asin, Laura

Saez, Berta

van Boven, Erica

Klaver, Siem

Swinkels, Dorine W.

Aben, Katja K.

Graif, Theresa

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland

[3] Ctr Clin & Basic Res AS, DK-2750 Ballerup, Denmark

[4] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[5] Univ Dundee, Ninewells Hosp & Med Sch, Div Med & Therapeut, Dundee DD1 9SY, Scotland

[6] Univ Dundee, Ninewells Hosp & Med Sch, Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 9SY, Scotland

[7] Howard Univ, Natl Human Genome Ctr, Dept Community & Family Med, Washington, DC 20060 USA

[8] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[9] Steno Diabet Ctr, DK-2820 Copenhagen, Denmark

[10] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark

[11] Glostrup Univ Hosp, Ctr Res Prevent & Hlth, DK-2600 Glostrup, Denmark

[12] Univ Zaragoza, Lozano Blesa Univ Hosp, Div Med Oncol, E-50009 Zaragoza, Spain

[13] Nanotechnol Inst Aragon, Inst Hlth Sci, Zaragoza 50009, Spain

[14] Univ Zaragoza, Lozano Blesa Univ Hosp, Div Radiat Oncol, E-50009 Zaragoza, Spain

[15] Maas Ziekenhuis, Dept Urol, NL-5830 AB Boxmeer, Netherlands

[16] Radboud Univ Nijmegen Med Ctr, Dept Clin Chem, NL-6500 HB Nijmegen, Netherlands

[17] Radboud Univ Nijmegen Med Ctr, Dept Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands

[18] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands

[19] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA

[20] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[21] Gelderse Vallei Hosp, Dept Urol, NL-6716 RP Ede, Netherlands

[22] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[23] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Lab Med, NL-9700 RB Groningen, Netherlands

[24] Maastricht Univ, Dept Mol Genet, NL-6200 MD Maastricht, Netherlands

[25] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands

[26] Univ Med Ctr Utrecht, Dept Biomed Genet, Complex Genet Sect, NL-3508 AB Utrecht, Netherlands

[27] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[28] Landspitali Univ Hosp, Dept Urol, IS-101 Reykjavik, Iceland

[29] Radboud Univ Nijmegen Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands

来源：

NATURE GENETICS | 2007年 / 39卷 / 08期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/ng2062

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 ( HNF1 beta), 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.

引用

页码：977 / 983

页数：7

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