title: Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.
abstract: In order to search for sequence variants conferring risk of thyroid cancer we conducted a genome-wide association study in 192 and 37,196 Icelandic cases and controls, respectively, followed by a replication study in individuals of European descent. Here we show that two common variants, located on 9q22.33 and 14q13.3, are associated with the disease. Overall, the strongest association signals were observed for rs965513 on 9q22.33 (OR = 1.75; P = 1.7 x 10(-27)) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 x 10(-9)). The gene nearest to the 9q22.33 locus is FOXE1 (TTF2) and NKX2-1 (TTF1) is among the genes located at the 14q13.3 locus. Both variants contribute to an increased risk of both papillary and follicular thyroid cancer. Approximately 3.7% of individuals are homozygous for both variants, and their estimated risk of thyroid cancer is 5.7-fold greater than that of noncarriers. In a study on a large sample set from the general population, both risk alleles are associated with low concentrations of thyroid stimulating hormone (TSH), and the 9q22.33 allele is associated with low concentration of thyroxin (T(4)) and high concentration of triiodothyronine (T(3)).
authors.affiliation: deCODE Genetics, Sturlugata 8, Reykjavik, Iceland. julius.gudmundsson@decode.is
authors.forename: Julius
authors.initials: J
authors.lastname: Gudmundsson
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: Asgeir
authors.initials: A
authors.lastname: Sigurdsson
authors.forename: Jon T
authors.initials: JT
authors.lastname: Bergthorsson
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Blondal
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.forename: Margret
authors.initials: M
authors.lastname: Jakobsdottir
authors.forename: Droplaug N
authors.initials: DN
authors.lastname: Magnusdottir
authors.forename: Sigurborg
authors.initials: S
authors.lastname: Matthiasdottir
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: Oskar B
authors.initials: OB
authors.lastname: Skarphedinsson
authors.forename: Hafdis
authors.initials: H
authors.lastname: Helgadottir
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nagy
authors.forename: Esperanza
authors.initials: E
authors.lastname: Aguillo
authors.forename: Eduardo
authors.initials: E
authors.lastname: Faure
authors.forename: Enrique
authors.initials: E
authors.lastname: Prats
authors.forename: Berta
authors.initials: B
authors.lastname: Saez
authors.forename: Mariano
authors.initials: M
authors.lastname: Martinez
authors.forename: Gudmundur I
authors.initials: GI
authors.lastname: Eyjolfsson
authors.forename: Unnur S
authors.initials: US
authors.lastname: Bjornsdottir
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Kristleifur
authors.initials: K
authors.lastname: Kristjansson
authors.forename: Michael L
authors.initials: ML
authors.lastname: Frigge
authors.forename: Hoskuldur
authors.initials: H
authors.lastname: Kristvinsson
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Thorvaldur
authors.initials: T
authors.lastname: Jonsson
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Hannes
authors.initials: H
authors.lastname: Hjartarsson
authors.forename: Jose I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Jon
authors.initials: J
authors.lastname: Hrafnkelsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014157:Transcription Factors; D014284:Triiodothyronine / Q000097:blood
chemical_list: D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; C504003:TTF1 protein, human; D014157:Transcription Factors; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine