Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.

2.50
Hdl Handle:
http://hdl.handle.net/2336/67655
Title:
Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.
Authors:
Gudmundsson, Julius; Sulem, Patrick; Gudbjartsson, Daniel F; Jonasson, Jon G; Sigurdsson, Asgeir; Bergthorsson, Jon T; He, Huiling; Blondal, Thorarinn; Geller, Frank; Jakobsdottir, Margret; Magnusdottir, Droplaug N; Matthiasdottir, Sigurborg; Stacey, Simon N; Skarphedinsson, Oskar B; Helgadottir, Hafdis; Li, Wei; Nagy, Rebecca; Aguillo, Esperanza; Faure, Eduardo; Prats, Enrique; Saez, Berta; Martinez, Mariano; Eyjolfsson, Gudmundur I; Bjornsdottir, Unnur S; Holm, Hilma; Kristjansson, Kristleifur; Frigge, Michael L; Kristvinsson, Hoskuldur; Gulcher, Jeffrey R; Jonsson, Thorvaldur; Rafnar, Thorunn; Hjartarsson, Hannes; Mayordomo, Jose I; de la Chapelle, Albert; Hrafnkelsson, Jon; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari
Citation:
Nat. Genet. 2009, 41(4):460-4
Issue Date:
1-Apr-2009
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)).
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/ng.339

Full metadata record

DC FieldValue Language
dc.contributor.authorGudmundsson, Julius-
dc.contributor.authorSulem, Patrick-
dc.contributor.authorGudbjartsson, Daniel F-
dc.contributor.authorJonasson, Jon G-
dc.contributor.authorSigurdsson, Asgeir-
dc.contributor.authorBergthorsson, Jon T-
dc.contributor.authorHe, Huiling-
dc.contributor.authorBlondal, Thorarinn-
dc.contributor.authorGeller, Frank-
dc.contributor.authorJakobsdottir, Margret-
dc.contributor.authorMagnusdottir, Droplaug N-
dc.contributor.authorMatthiasdottir, Sigurborg-
dc.contributor.authorStacey, Simon N-
dc.contributor.authorSkarphedinsson, Oskar B-
dc.contributor.authorHelgadottir, Hafdis-
dc.contributor.authorLi, Wei-
dc.contributor.authorNagy, Rebecca-
dc.contributor.authorAguillo, Esperanza-
dc.contributor.authorFaure, Eduardo-
dc.contributor.authorPrats, Enrique-
dc.contributor.authorSaez, Berta-
dc.contributor.authorMartinez, Mariano-
dc.contributor.authorEyjolfsson, Gudmundur I-
dc.contributor.authorBjornsdottir, Unnur S-
dc.contributor.authorHolm, Hilma-
dc.contributor.authorKristjansson, Kristleifur-
dc.contributor.authorFrigge, Michael L-
dc.contributor.authorKristvinsson, Hoskuldur-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorJonsson, Thorvaldur-
dc.contributor.authorRafnar, Thorunn-
dc.contributor.authorHjartarsson, Hannes-
dc.contributor.authorMayordomo, Jose I-
dc.contributor.authorde la Chapelle, Albert-
dc.contributor.authorHrafnkelsson, Jon-
dc.contributor.authorThorsteinsdottir, Unnur-
dc.contributor.authorKong, Augustine-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2009-05-08T11:43:38Z-
dc.date.available2009-05-08T11:43:38Z-
dc.date.issued2009-04-01-
dc.date.submitted2009-05-08-
dc.identifier.citationNat. Genet. 2009, 41(4):460-4en
dc.identifier.issn1546-1718-
dc.identifier.pmid19198613-
dc.identifier.doi10.1038/ng.339-
dc.identifier.urihttp://hdl.handle.net/2336/67655-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractIn 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)).en
dc.language.isoenen
dc.publisherNature Pub. Co.en
dc.relation.urlhttp://dx.doi.org/10.1038/ng.339en
dc.subject.meshPubMed - in processen
dc.titleCommon variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations.en
dc.typeArticleen
dc.contributor.departmentdeCODE Genetics, Sturlugata 8, Reykjavik, Iceland. julius.gudmundsson@decode.isen
dc.identifier.journalNature geneticsen

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