Unknown

Dataset Information

0

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)).

SUBMITTER: Gudmundsson J 

PROVIDER: S-EPMC3664837 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Gudmundsson Julius J   Sulem Patrick P   Gudbjartsson Daniel F DF   Jonasson Jon G JG   Sigurdsson Asgeir A   Bergthorsson Jon T JT   He Huiling H   Blondal Thorarinn T   Geller Frank F   Jakobsdottir Margret M   Magnusdottir Droplaug N DN   Matthiasdottir Sigurborg S   Stacey Simon N SN   Skarphedinsson Oskar B OB   Helgadottir Hafdis H   Li Wei W   Nagy Rebecca R   Aguillo Esperanza E   Faure Eduardo E   Prats Enrique E   Saez Berta B   Martinez Mariano M   Eyjolfsson Gudmundur I GI   Bjornsdottir Unnur S US   Holm Hilma H   Kristjansson Kristleifur K   Frigge Michael L ML   Kristvinsson Hoskuldur H   Gulcher Jeffrey R JR   Jonsson Thorvaldur T   Rafnar Thorunn T   Hjartarsson Hannes H   Mayordomo Jose I JI   de la Chapelle Albert A   Hrafnkelsson Jon J   Thorsteinsdottir Unnur U   Kong Augustine A   Stefansson Kari K  

Nature genetics 20090206 4


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  ...[more]

Similar Datasets

| S-EPMC4354996 | biostudies-literature
| S-EPMC4388539 | biostudies-literature
| S-EPMC8725568 | biostudies-literature
| S-EPMC5330385 | biostudies-literature
| S-EPMC6511513 | biostudies-literature
| S-EPMC3518668 | biostudies-literature
| S-EPMC3682231 | biostudies-literature
| S-EPMC4499475 | biostudies-literature
| S-EPMC5603517 | biostudies-literature
| S-EPMC6074950 | biostudies-literature