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The Common Genetic Variant rs944289 on Chromosome 14q13.3 Associates with Risk of Both Malignant and Benign Thyroid Tumors in the Japanese Population

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Title: The Common Genetic Variant rs944289 on Chromosome 14q13.3 Associates with Risk of Both Malignant and Benign Thyroid Tumors in the Japanese Population
Authors: Rogounovitch, Tatiana I. / Bychkov, Andrey / Takahashi, Meiko / Mitsutake, Norisato / Nakashima, Masahiro / Nikitski, Alyaksandr V. / Hayashi, Tomayoshi / Hirokawa, Mitsuyoshi / Ishigaki, Katsu / Shigematsu, Kazuto / Bogdanova, Tetiana / Matsuse, Michiko / Nishihara, Eijun / Minami, Shigeki / Yamanouchi, Kosho / Ito, Masahiro / Kawaguchi, Takahisa / Kondo, Hisayoshi / Takamura, Noboru / Ito, Yasuhiro / Miyauchi, Akira / Matsuda, Fumihiko / Yamashita, Shunichi / Saenko, Vladimir A.
Issue Date: 9-Mar-2015
Publisher: Mary Ann Liebert Inc.
Citation: Thyroid, 25(3), pp.333-340; 2015
Abstract: Background: Several single nucleotide polymorphisms (SNP) have been identified to be associated with the risk for differentiated thyroid cancer in populations of distinct ethnic background. The relationship of these genetic markers to a benign tumor of the thyroid, follicular adenoma (FA), is not well established. Methods: In a multicenter retrospective case-control study, five thyroid cancer-related SNPs - rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B) - were genotyped in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls. Results: A significant association was found between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000]) and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302 (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI 1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980-1.316]) in this series. A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC (about 10% decrease per each risk allele). NRG1 expression also significantly correlated with that of PTCSC3. Conclusions: Association of rs944289, which was previously known to confer risk for thyroid cancer, with FA, and the correlation between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and imply broader roles of the pathways they underlie in thyroid tumorigenesis, not limited to carcinogenesis.
Keywords: follicular adenoma / papillary thyroid carcinoma / single nucleotide 179 polymorphism / genotype / case-control association study
URI: http://hdl.handle.net/10069/35265
ISSN: 10507256
DOI: 10.1089/thy.2014.0431
Rights: © Mary Ann Liebert, Inc. 2015. / Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/thy.2014.0431
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/35265

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