Do thyroid cancer risk factors FOXE1 and NKX2-1 influence risk of development of a benign adenoma?

• Project/Area Number: 24591369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagasaki University
• Principal Investigator: SAENKO Vladimir 長崎大学, 原爆後障害医療研究所, 准教授 (30343346)
• Co-Investigator(Kenkyū-buntansha): NAKASHIMA Masahiro 長崎大学, 原爆後障害医療研究所, 教授 (50284683) ; MITSUTAKE Norisato 長崎大学, 原爆後障害医療研究所, 准教授 (50404215) ; ITO Masahiro 独立行政法人国立病院機構, 長崎医療センター 臨床検査科, 部長 (30184691)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内分泌学 / 甲状腺腫瘍 / 遺伝子多型

Outline of Final Research Achievements

Association analysis of five SNPs previously reported to confer risk for thyroid cancer with benign follicular adenoma (FA) was performed in 959 FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls from Japan.
A significant association was found between FA and rs944289 (PTCSC3) and rs2439302 (NRG1), demonstrating that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and implying broader roles of the pathways that NRG1 and PTCSC3 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, Nishihara 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 Issue: 3 Pages: 333-340
  • DOI: 10.1089/thy.2014.0431
  • NAID: 120006987147
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Patterns of FOXE1 expression in papillary thyroid carcinoma by immunohistochemistry. (2013)
  • Author(s): Bychkov A
  • Journal Title: Thyroid Volume: 未定 Issue: 7 Pages: 817-828
  • DOI: 10.1089/thy.2012.0466
  • Peer Reviewed
• [Journal Article] Functional characterization of the novel BRAF complex mutation, BRAF(V600delinsYM), identified in papillary thyroid carcinoma. (2013)
  • Author(s): Matsuse, M.
  • Journal Title: Int. J. Cancer Volume: 132 Issue: 3 Pages: 738-743
  • DOI: 10.1002/ijc.27709
  • Peer Reviewed
• [Journal Article] Copy number alteration and uniparental disomy analysis categorizes Japanese papillary thyroid carcinomas into distinct groups (2012)
  • Author(s): Matsuse M, Suzuki K, Saenko V, Mitsutake N, Yamashita S, et al
  • Journal Title: PLoS One Volume: 7(4) Issue: 4 Pages: e36063-e36063
  • DOI: 10.1371/journal.pone.0036063
  • NAID: 120006985474
  • Peer Reviewed
• [Journal Article] Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report (2012)
  • Author(s): Stanojevic B, Dzodic R, Saenko V, Milovanovic Z, Krstevski V, Radlovic P, Buta M, Rulic B, Todorovic L, Dimitrijevic B, Yamashita S
  • Journal Title: BMC Cancer Volume: 12(1) Issue: 1 Pages: 224-224
  • DOI: 10.1186/1471-2407-12-224
  • Peer Reviewed
• [Journal Article] Surgical management of primary thyroid carcinoma arising in thyroglossal duct cyst: An experience of a single institution in Serbia (2012)
  • Author(s): Dzodic R
  • Journal Title: Endocrine Journal Volume: 59 Issue: 6 Pages: 517-522
  • DOI: 10.1507/endocrj.EJ12-0070
  • NAID: 10030816898
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts (2012)
  • Author(s): Kashiyama K, Mitsutake N, Matsuse M, Ogi T, Saenk V, Ujifuku K, Utani A, Hirano A, Yamashita S
  • Journal Title: J Invest Dermatol Volume: 132(6) Issue: 6 Pages: 1597-1604
  • DOI: 10.1038/jid.2012.22
  • NAID: 120006985401
  • Peer Reviewed
• [Journal Article] Imatinib enhances docetaxel-induced apoptosis through inhibition of nuclear factor-kB activation in anaplastic thyroid carcinoma cells (2012)
  • Author(s): Kim E, Matsuse M, Saenko V, Suzuki K, Ohtsuru A, Mitsutake N, Yamashita S
  • Journal Title: Thyroid Volume: 22(7) Pages: 717-724
  • DOI: 10.1089/thy.2011-0380
  • Peer Reviewed
• [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
• [Presentation] Association of the NRG1 gene with risk for developing thyroid cancer after Chernobyl. (2013)
  • Author(s): Saenko V, Takahashi M, Rogounovitch T, Drozd V, Demidchik Yu, Bogdanova T, Tronko M, Mitsutake N, Takamura N, Takahashi J, Matsuda F, Yamashita S
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター（宮城）
• [Presentation] Association of three polymorphisms of the FOXE1 gene with papillary thyroid carcinoma in Belarussian and Japanese populations. (2013)
  • Author(s): サエンコ ウラジミール, 高橋めい子, ログノビッチ タチアナ, ドロズド ワレンチナ, ビチコブ アンドレイ, 川口喬久, 光武範吏, 廣川満良, 西原永潤, 宮内昭, 吉浦孝一郎, 松田文彦, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館（和歌山）
• [Presentation] Genetic polymorphism on chromosome 14q13.3 associates with risk for thyroid follicular adenoma in Japanese patients. (2013)
  • 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, 光武範吏, 伊東正博, 松田文彦, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館（和歌山）
• [Presentation] Transcriptional activities of FOXE1 polyalanine tract variants. (2013)
  • Author(s): ニキツキ― アリャクサンドル, サエンコ ウラジミール, ビチコブ アンドレイ, ログノビッチ タチアナ, 光武範吏, 山下俊一
  • Organizer: 第56回日本甲状腺学会学術集会
  • Place of Presentation: 和歌山県民文化会館（和歌山
• [Presentation] Differential expression of FOXE1 at tumor/host interface in papillary thyroid carcinoma (2012)
  • Author(s): Andrey Bychkov
  • Organizer: 第16回日本内分泌病理学会学術集会
  • Place of Presentation: 東北大学 艮陵会館（宮城県）
• [Presentation] Incidence of Hashimoto Thyroiditis on Ultrasound Screening in Russia (2012)
  • Author(s): Vladimir Parshin
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
• [Presentation] Indentification of Genes Cooperating with Mutant BRAF in Thyroid Carcinogenesis (2012)
  • Author(s): Tatiana Rogounovitch
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
• [Presentation] Clinical and Genetic Correlations of Immunohistochemical Foxe1 Expression in PTC in Japanese Patients (2012)
  • Author(s): Andrey Bychkov
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
• [Presentation] Radiation Induced Thyroid Carcinogenesis (2012)
  • Author(s): Vladimir Saenko
  • Organizer: 10th Asia and Oceania Thyroid Association Congress
  • Place of Presentation: Bali, Indonesia
  • Invited
• [Presentation] ウクライナ成人の甲状腺乳頭癌の組織像は本邦症例と異なるのか？ (2012)
  • Author(s): 伊藤正博
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: アクロス福岡（福岡県）
• [Presentation] Relationship of immunohistochemical FOXE1 expression to clinical features and genetics in PTC (2012)
  • Author(s): ビチコブ アンドレイ
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: アクロス福岡（福岡県）
• [Presentation] Molecular epidemiology study of Chernobyl thyroid cancer in an extended sample set from Belarus and Ukraine (2012)
  • Author(s): サエンコ ウラジミール
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: アクロス福岡（福岡県）
• [Presentation] Incidence of Hashimoto Thyroiditis on Ultrasound Screening in Russia (2012)
  • Author(s): パーシン ウラジミール
  • Organizer: 第55回日本甲状腺学会
  • Place of Presentation: アクロス福岡（福岡県）
• [Presentation] Radiation and thyroid cancer (2012)
  • Author(s): Vladimir Saenko
  • Organizer: 25th International Symposium on Cancer Research
  • Place of Presentation: 国立がん研究センター 国際研究交流会館（東京都）
  • Invited
• [Presentation] Radiation and Thyroid Cancer
  • Author(s): Vladimir Saenko
  • Organizer: 第26回環境ホルモン学会講演会
  • Place of Presentation: 東京大学 山上会館（東京都）
  • Invited
• [Book] THYROID CANCER IN UKRAINE AFTER CHERNOBYL dosimetry, epidemiology, pathology, molecular biology (2014)
  • Author(s): Tronko M, Bogdanova T, Saenko V, Thomas GA, Likhtarov I, Yamashita S
  • Total Pages: 175
  • Publisher: 長崎・ヒバクシャ医療国際協力会（Nagasaki Association for Hibakushas' Medical Care: NASHIM)
• [Remarks] 長崎大学 原研疫学
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/dhrc/
• [Remarks] 長崎大学原研リスクホームページ
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/dhrc/
• [Remarks] 長崎大学原研リスク
  • URL: http://www-sdc.med.nagasaki-u.ac.jp/dhrc/