Journal Article

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

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

2009

Overview

Julius Gudmundsson and colleagues report the association of two SNPs on chromosomes 9 and 14 with thyroid cancer in European populations. The variants are near FOXE1 and NKX2-1 , both good biological candidates, and individuals who are homozygous for both risk variants have a 5.7-fold greater risk of thyroid cancer. 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 (T 4 ) and high concentration of triiodothyronine (T 3 ).

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosome Mapping / Chromosomes, Human, Pair 4 / Chromosomes, Human, Pair 9 / DNA-Binding Proteins - genetics / Endocrinopathies / Europe - epidemiology / Females / Forkhead Transcription Factors - genetics / Fundamental and applied biological sciences. Psychology / Gene Function / Genetic aspects / Genetic Predisposition to Disease - genetics / Genetic Variation / Genetics of eukaryotes. Biological and molecular evolution / Human Genetics / Humans / letter / Malignant tumors / Medical sciences / Multivariate analysis / Non tumoral diseases. Target tissue resistance. Benign neoplasms / Population / Risk factors / Sample size / Statistics / Thyroid / Thyroid cancer / Thyroid gland / Thyroid Neoplasms - epidemiology / Thyroid Neoplasms - genetics / Thyroid. Thyroid axis (diseases) / Thyrotropin - blood / Thyroxine - blood / Transcription Factors / Triiodothyronine - blood