Letter abstract
Nature Genetics 41, 460 - 464 (2009)
Published online: 6 February 2009 | doi:10.1038/ng.339
Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations
Julius Gudmundsson1,16, Patrick Sulem1,16, Daniel F Gudbjartsson1, Jon G Jonasson2,3,4, Asgeir Sigurdsson1, Jon T Bergthorsson1, Huiling He5, Thorarinn Blondal1, Frank Geller1, Margret Jakobsdottir1, Droplaug N Magnusdottir1, Sigurborg Matthiasdottir1, Simon N Stacey1, Oskar B Skarphedinsson1, Hafdis Helgadottir1, Wei Li5, Rebecca Nagy5, Esperanza Aguillo6, Eduardo Faure6, Enrique Prats7, Berta Saez8, Mariano Martinez9, Gudmundur I Eyjolfsson10, Unnur S Bjornsdottir3, Hilma Holm1,11, Kristleifur Kristjansson1, Michael L Frigge1, Hoskuldur Kristvinsson12, Jeffrey R Gulcher1, Thorvaldur Jonsson3,12, Thorunn Rafnar1, Hannes Hjartarsson13, Jose I Mayordomo8,14, Albert de la Chapelle5, Jon Hrafnkelsson15, Unnur Thorsteinsdottir1,3, Augustine Kong1 & Kari Stefansson1,3
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 
10-27) and rs944289 on 14q13.3 (OR = 1.37; P = 2.0 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 (T4) and high concentration of triiodothyronine (T3).
- deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
- Department of Pathology, Landspitali-University Hospital Hringbraut, 101 Reykjavik, Iceland.
- Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
- The Icelandic Cancer Registry, 105 Reykjavik, Iceland.
- Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
- Division of Endocrinology, University Hospital, 50009 Zaragoza, Spain.
- Division of Nuclear Medicine, University Hospital, 50009 Zaragoza, Spain.
- The Health Science Institute, Nanotechnology Institute of Aragon, 50009 Zaragoza, Spain.
- Division of Surgery, University Hospital, 50009 Zaragoza, Spain.
- The Laboratory in Mjodd, 109 Reykjavik, Iceland.
- Department of Internal Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
- Department of Surgery, Landspitali-University Hospital Hringbraut, 101 Reykjavik, Iceland.
- ORL, H&N Surgery Department, Landspitali-University Hospital Fossvogi, 108 Reykjavik, Iceland.
- Division of Medical Oncology, Lozano Blesa University Hospital, University of Zaragoza, 50009 Zaragoza, Spain.
- Department of Oncology, Landspitali-University Hospital Hringbraut, 101 Reykjavik, Iceland.
- These authors contributed equally to this work.
Correspondence to: Kari Stefansson1,3 e-mail: kstefans@decode.is
Correspondence to: Julius Gudmundsson1,16 e-mail: julius.gudmundsson@decode.is
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