甲状腺癌リスク因子ＦＯＸＥ１とＮＫＸ２－１は良性腺腫形成にも関連するのか

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24591369
• Research Institution: Nagasaki University
• Principal Investigator: サエンコ ウラジミール 長崎大学, 原爆後障害医療研究所, 准教授 (30343346)
• Co-Investigator(Kenkyū-buntansha): 中島 正洋 長崎大学, 原爆後障害医療研究所, 教授 (50284683) ; 光武 範吏 長崎大学, 原爆後障害医療研究所, 准教授 (50404215) ; 伊東 正博 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床検査科, 部長 (30184691)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 内分泌学 / 甲状腺腫瘍 / 遺伝子多型

Outline of Annual Research Achievements

The association of five single-nucleotide polymorphisms (SNPs): rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1) and rs6983267 (8q24, POU5F1B), which have been previously reported to confer risk for thyroid cancer, with a benign tumor of the thyroid, the follicular adenoma (FA) was accomplished, in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls from Japan.
A significant association was found between FA and rs944289 (p=0.002; OR=1.176), and suggestively with rs2439302 (p=0.033; OR=1.149). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR=1.587) and rs944289 (p=0.003; OR=1.234), newly found in the Japanese population for rs2439302 (p=0.003; OR=1.266) and rs1867277 (p=1.17E-04; OR=1.492), and was not replicated for rs6983267 (p=0.082). A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC indicating about a 10% decrease per each risk allele. NRG1 expression also significantly correlated with that of PTCSC3. The results are published (Rogounovitch et al., Thyroid, 2015).
The 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.

Research Products

• [Journal Article] The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population. (2015)
  • Author(s): Rogounovitch TI, Bychkov A, Takahashi M, Mitsutake N, Nakashima M, Nikitski AV, Hayashi T, Hirokawa M, Ishigaki K, Shigematsu K, Bogdanova T, Matsuse M, Nakahara E, Minami S, Yamanouchi K, Ito M, Kawaguchi T, Kondo H, Takamura N, Ito Y, Miyauchi A, Matsuda F, Yamashita S, Saenko VA
  • Journal Title: Thyroid Volume: 25 Pages: 333-340
  • DOI: 10.1089/thy.2014.0431
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Rare T allele of rs944289 associates not only with risk of malignant but also of benign thyroid tumors (2014)
  • Author(s): ログノビッチ タチアナ, サエンコ ウラジミール, ビチコブ アンドレイ, ニキツキ― アリャクサンドル, 高橋めい子, 中島正洋, 林徳眞吉, 廣川満良, 宮内昭, 石垣克, 重松和人, 松瀬美智子, 光武範吏, 西原永潤, 南恵樹, 山内孝彰, 伊東正博, 吉浦孝一郎, 松田文彦, 山下俊一
  • Organizer: 第87回 日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場・福岡サンパレス（福岡県・福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Association of polymorphism in the FOXE1 gene locus with papillary thyroid carcinoma in Japanese patients (2014)
  • Author(s): V.Saenko, T.Rogounovitch, A.Bychkov, N.Mitsutake, M.Matsuse, E.Nishihara, M.Hirokawa, A.Nikitsky, S.Minami, K.Yamanouchi, K.Yoshiura, A.Miyauchi, S.Yamashita
  • Organizer: 第87回 日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場・福岡サンパレス（福岡県・福岡市）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Remarks] 長崎大学 原研疫学
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/dhrc/