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.
authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. julius.gudmundsson@decode.is
authors.forename: Julius
authors.initials: J
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authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Steinthorsdottir
authors.forename: Jon T
authors.initials: JT
authors.lastname: Bergthorsson
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Daniel
authors.initials: D
authors.lastname: Gudbjartsson
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authors.initials: A
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authors.initials: A
authors.lastname: Sigurdsson
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authors.lastname: Benediktsdottir
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authors.initials: M
authors.lastname: Jakobsdottir
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authors.lastname: Helgason
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authors.forename: Peter C Y
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authors.lastname: Tong
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authors.lastname: Andersen
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authors.lastname: Borch-Johnsen
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authors.lastname: Swinkels
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authors.initials: KK
authors.lastname: Aben
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authors.lastname: Graif
authors.forename: John
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authors.lastname: Cashy
authors.forename: Brian K
authors.initials: BK
authors.lastname: Suarez
authors.forename: Onco
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authors.lastname: van Vierssen Trip
authors.forename: Michael L
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authors.lastname: Frigge
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authors.lastname: Ober
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authors.lastname: Christiansen
authors.forename: Daniel J
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authors.lastname: Rader
authors.forename: Colin N A
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authors.lastname: Palmer
authors.forename: Charles
authors.initials: C
authors.lastname: Rotimi
authors.forename: Juliana C N
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authors.lastname: Chan
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
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authors.lastname: Kong
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authors.initials: K
authors.lastname: Stefansson
mesh_terms: D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta