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

• Published in: Nature genetics Vol. 39; no. 8; pp. 977 - 983
• Main Authors: Borch-Johnsen, Knut, Ghosh, Shyamali, Tong, Peter C Y, Sigurdsson, Asgeir, Asin, Laura, So, Wing-Yee, Hofker, Marten H, Ober, Carole, Jonsson, Eirikur, Palmer, Colin N A, Saez, Berta, Kimber, Charlotte H, Frigge, Michael L, Barkardottir, Rosa B, Agnarsson, Bjarni A, Suarez, Brian K, Bagger, Yu, Wilensky, Robert L, Stacey, Simon N, Swinkels, Dorine W, Hansen, Torben, Einarsson, Gudmundur V, Benediktsdottir, Kristrun R, Gulcher, Jeffrey R, Gudmundsson, Julius, Wijmenga, Cisca, Sigurdsson, Gunnar, Morris, Andrew D, Thorsteinsdottir, Unnur, Tres, Alejandro, Olafsdottir, Adalheidur, Baker, Adam, Magnusdottir, Dana, Chen, Yuanxiu, Thorleifsson, Gudmar, Adeyemo, Adebowale, Fuertes, Fernando, Kong, Augustine, Jakobsdottir, Margret, Kiemeney, Lambertus A, Ng, Maggie C Y, Kristinsson, Kari T, Stefansson, Kari, Klaver, Siem, van Vierssen Trip, Onco, Chan, Juliana C N, Aben, Katja K, Benediktsson, Rafn, Birgisdottir, Birgitta, Blondal, Thorarinn, Jorgensen, Torben, Thorlacius, Steinunn, Stefansdottir, Gerdur, Gudbjartsson, Daniel, Zhou, Jie, Rotimi, Charles, Ruiz-Echarri, Manuel, Mayordomo, Jose I, Helgason, Agnar, Rader, Daniel J, Pedersen, Oluf, Gunnarsdottir, Steinunn, Reilly, Muredach P, van Boven, Erica, Rafnar, Thorunn, Bergthorsson, Jon T, Kristjansson, Kristleifur, Cashy, John, Catalona, William J, Sulem, Patrick, Steinthorsdottir, Valgerdur, Andersen, Gitte, Manolescu, Andrei, Christiansen, Claus, Graif, Theresa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.08.2007
• Subjects: Biological and medical sciences; Case-Control Studies; Chromosomes, Human, Pair 17; Diabetes Mellitus, Type 2 - genetics; Diagnosis; Fundamental and applied biological sciences. Psychology; Genetic aspects; Genetic Predisposition to Disease; Genetic variation; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Gynecology. Andrology. Obstetrics; Haplotypes; Health risks; Hepatocyte Nuclear Factor 1-beta - genetics; Humans; Male; Male genital diseases; Medical sciences; Mutation; Nephrology. Urinary tract diseases; Physiological aspects; Polymorphism, Single Nucleotide; Population genetics; Prostate cancer; Prostatic Neoplasms - genetics; Risk factors; Tumors; Tumors of the urinary system; Type 2 diabetes; Urinary tract. Prostate gland; Netherlands; Endocrinopathy; Type 2 diabetes; Variant; Urinary system disease; Prostate disease; Metabolic diseases; Risk; Malignant tumor; Male genital diseases; Prostate cancer; Chromosome 17
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng2062

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.