17号染色体上的两个变异体增加患前列腺癌的风险，而位于转录因子7类似物2（TCF2）基因中的那个变异体则可预防2型糖尿病。

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

作者信息

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, Cashy John, Suarez Brian K, van Vierssen Trip Onco, Frigge Michael L, Ober Carole, Hofker Marten H, Wijmenga Cisca, Christiansen Claus, Rader Daniel J, Palmer Colin N A, Rotimi Charles, Chan Juliana C N, Pedersen Oluf, Sigurdsson Gunnar, Benediktsson Rafn, Jonsson Eirikur, Einarsson Gudmundur V, Mayordomo Jose I, Catalona William J, Kiemeney Lambertus A, Barkardottir Rosa B, Gulcher Jeffrey R, Thorsteinsdottir Unnur, Kong Augustine, Stefansson Kari

机构信息

deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

出版信息

Nat Genet. 2007 Aug;39(8):977-83. doi: 10.1038/ng2062. Epub 2007 Jul 1.

DOI:10.1038/ng2062

PMID:17603485

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.

摘要

我们进行了一项全基因组关联扫描，以寻找导致前列腺癌风险的序列变异，研究对象为1501名冰岛前列腺癌男性患者和11290名对照者。涉及另外三个病例对照组的后续研究重复证实了17号染色体上两个变异与该疾病的关联。这两个变异相距33兆碱基，位于先前基于家系的前列腺癌连锁研究中涉及的一个区域内。这些变异各自带来的风险适中（等位基因优势比约为1.20），但由于它们很常见，其共同的人群归因风险相当大。其中一个变异位于TCF2（HNF1β）基因中，已知该基因在患有青年型5型成年发病糖尿病的个体中发生突变。包括一个西非组和一个中国组在内的八个病例对照组的结果表明，该变异对2型糖尿病具有保护作用。