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Molecular epidemiological study of radiation-induced juvenile thyroid cancer

Research Project

Project/Area Number 19K07471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Nagasaki Medical Center

Principal Investigator

Ito Masahiro  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, 病理医 (30184691)

Co-Investigator(Kenkyū-buntansha) 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)
中島 正洋  長崎大学, 原爆後障害医療研究所, 教授 (50284683)
三浦 史郎  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), 病理診断科, がん中央診療部長・がんゲノム診療部長 (80513316)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords小児甲状腺癌 / 甲状腺癌 / 放射線被曝 / チェルノブイリ / 福島原発事故 / BRAF / 小児 / 遺伝子変異 / 分子疫学
Outline of Research at the Start

福島第一原発事故後,若年者の甲状腺スクリーニングは世界で初め実施され予想を越える甲状腺癌症例が発見された。その甲状腺癌の増加が放射線の影響かスクリーニング効果か結論は出ていない。チェルノブイリ事故後に多発した小児甲状腺がんでゲノム解析がなされてきたが、放射線特異的な遺伝子異常は未だ見いだされていない。本研究ではチェルノブイリ症例に加えて、福島第一原発事故後に周辺地域の検診で発見され切除された症例を加え、二つの異なる地域と異なる被曝線量を背景とした若年被曝による放射線誘発甲状腺がんの高リスク分子機構を、ゲノムDNA変異解析に加えエピジェネティックな変異解析の両面から解明することを目的としている。

Outline of Final Research Achievements

In the morphological analysis of juvenile-onset thyroid cancers after the Fukushima Daiichi NPP accident, most cases were classical subtype papillary carcinomas with BRAF point mutations (Cancer Sci 2019). Furthermore, the pathological characteristics of a total of 748 cases (Ukraine 410, Japan 338), including young-onset thyroid cancer after the Chernobyl accident, spontaneous thyroid cancer in Ukraine, spontaneous thyroid cancer in Japan, and young-onset cases in Fukushima prefecture, were analyzed by age groups. Chernobyl pediatric cases had frequently solid components and were highly invasive. There was no significant morphological difference between the Japanese two groups. But the male-female ratio was close to 1: 1 and the average tumor diameter was small (Thyroid 2021).

Academic Significance and Societal Importance of the Research Achievements

福島第一原発事故後の若年発症甲状腺癌とチェルノブイリ原発事故後に激増した小児甲状腺癌の病理形態学的な比較,本邦の自然発症性若年者甲状腺癌とチェルノブイリ周辺地域の自然発症性若年者甲状腺癌の比較がなされたことはなく,本研究課題は独自性の高いと云える。本研究から期待される成果は以下の4点にある。1. 地域や環境の差が病理形態学的所見や遺伝子変異に与える影響の解明。2.低線量被曝関連の若年者甲状腺発癌機構の解明。福島第一原発事故後に発見された若年者甲状腺癌と低線量被曝の因果関係の解明。3. 若年者の自然発症性甲状腺がんの発症機序の解明。4.原子力発電所事故時の防護を考える上での基礎的なデータとなる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (43 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (8 results) Journal Article (23 results) (of which Int'l Joint Research: 11 results,  Peer Reviewed: 23 results,  Open Access: 17 results) Presentation (9 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] チェルノブイリ組織バンク(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] キエフ内分泌研究所(ウクライナ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] MRRC, Russia(ロシア連邦)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] キエフ内分泌研究所(ウクライナ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] キエフ内分泌研究所(ウクライナ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ロンドン大学(英国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] カトリック大学(イタリア)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ロシア医科学アカデミー医学放射線研究センター(ロシア連邦)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident2022

    • Author(s)
      Zurnadzhy L, Bogdanova T, Rogounovitch TI, Ito M, Tronko M, Yamashita S, Mitsutake N, Chernyshov S, Masiuk S, Saenko VA.
    • Journal Title

      Front. Med., 26 April 2022

      Volume: - Pages: 882727-882727

    • DOI

      10.3389/fmed.2022.882727

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] rs9459874 and rs1012656 in CCR6/FGFR1OP confer susceptibility to primary biliary cholangitis2022

    • Author(s)
      Hitomi Yuki、Aiba Yoshihiro、Ueno Kazuko、Nishida Nao、Kawai Yosuke、Kawashima Minae、Yasunami Michio、Gervais Olivier、Ito Masahiro、Cordell Heather J.、Mells George F.、Nagasaki Masao、Tokunaga Katsushi、Tsuiji Makoto、Nakamura Minoru
    • Journal Title

      Journal of Autoimmunity

      Volume: 126 Pages: 102775-102775

    • DOI

      10.1016/j.jaut.2021.102775

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The BRAF V600E Mutation Is Not a Risk Factor for More Aggressive Tumor Behavior in Radiogenic and Sporadic Papillary Thyroid Carcinoma at a Young Age.2021

    • Author(s)
      Zurnadzhy L, Bogdanova T, Rogounovitch TI, Ito M, Tronko M, Yamashita S, Mitsutake N, Chernyshov S, Masiuk S, Saenko VA.
    • Journal Title

      Cancers (Basel).

      Volume: 13 Issue: 23 Pages: 6038-6038

    • DOI

      10.3390/cancers13236038

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Introduction of histological classification and cytology reporting format of the Japanese General Rules for the Description of Thyroid Cancer with a special focus on the differences of the WHO Histological Classification and The Bethesda System of Thyroid Cytology2021

    • Author(s)
      Sakamoto A, Hirokawa M, Ito M, Naganuma H, Suzuki O, Hashimoto Y, Suzuki S, Shimura H.
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 6 Pages: 621-630

    • DOI

      10.1507/endocrj.EJ21-0077

    • NAID

      130008057574

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significance of abnormal 53BP1 expression as a novel molecular pathologic parameter of follicular-shaped B-cell lymphoid lesions in human digestive tract2021

    • Author(s)
      Hanh Luong Thi My、Matsuda Katsuya、Niino Daisuke、Kurohama Hirokazu、Ito Masahiro、Nakashima Masahiro
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 3074-3074

    • DOI

      10.1038/s41598-021-82867-0

    • NAID

      120006980735

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.2021

    • Author(s)
      Morton LM, Bogdanova TI, Thomas GA, Tronko MD, Getz G, Chanock SJ.
    • Journal Title

      Science.

      Volume: 14 Issue: 6543

    • DOI

      10.1126/science.abg2538

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.2021

    • Author(s)
      Kurohama H, Matsuda K, Kishino M, Yoshino M, Yamaguchi Y, Matsuu-Matsuyama M, Kondo H, Mitsutake N, Kinoshita A, Yoshiura KI, Nakashima M.
    • Journal Title

      J Radiat Res.

      Volume: 62 Issue: Supplement_1 Pages: i78-i87

    • DOI

      10.1093/jrr/rraa139

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Papillary thyroid carcinoma in Ukraine after Chernobyl and in Japan after Fukushima: different histopathological scenarios.2020

    • Author(s)
      Bogdanova TI, Saenko VA, Hashimoto Y, Hirokawa M, Zurnadzhy LY, Hayashi T, Ito M, Iwadate M, Mitsutake N, Rogounovitch T, Sakamoto A, Naganuma H, Miyauchi A, Tronko MD, Thomas G, Yamashita S, Suzuki S:
    • Journal Title

      Thyroid

      Volume: 308 Issue: 9 Pages: 1-13

    • DOI

      10.1089/thy.2020.0308

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Clinicopathological Results of Thyroid Cancer With BRAFV600E Mutation in the Young Population of Fukushima.2020

    • Author(s)
      Iwadate M, Mitsutake N, Matsuse M, Fukushima T, Suzuki S, Matsumoto Y, Ookouchi C, Mizunuma H, Nakamura I, Nakano K, Sakamoto A, Hirokawa M, Ito M, Naganuma H, Hashimoto Y, Shimura H, Yamashita S, Suzuki S
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 105 Issue: 12 Pages: 573-573

    • DOI

      10.1210/clinem/dgaa573

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors.2020

    • Author(s)
      Mussazhanova Z, Shimamura M, Kurashige T, Ito M, Nakashima M, Nagayama Y
    • Journal Title

      Cancer Sci.

      Volume: 111 Issue: 8 Pages: 2814-2823

    • DOI

      10.1111/cas.14501

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum kynurenine levels are a novel biomarker to predict the prognosis of patients with hepatocellular carcinoma.2020

    • Author(s)
      Bekki S, Hashimoto S, Yamasaki K, Komori A, Abiru S, Nagaoka S, Saeki A, Suehiro T, Kugiyama Y, Beppu A, Kuroki T, Nakamura M, Ito M, Yatsuhashi H
    • Journal Title

      PLoS One

      Volume: 15 Issue: 10 Pages: e0241002-e0241002

    • DOI

      10.1371/journal.pone.0241002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Incidence, predictive factors and severity of methotrexate-related liver injury in rheumatoid arthritis: a longitudinal cohort study.2020

    • Author(s)
      Mori S, Arima N, Ito M, Ueki Y, Abe Y, Aoyagi K, Fujiyama S
    • Journal Title

      Rheumatol Adv Pract.

      Volume: 4 Issue: 2

    • DOI

      10.1093/rap/rkaa020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acceleration of BRAFV600E-mediated thyroid carcinogenesis by TGFβ signal deficiency.2020

    • Author(s)
      Shimamura M, Kurashige T, Kuatov R, Nagayama Y.
    • Journal Title

      Endocrine

      Volume: in press Issue: 3 Pages: 571-577

    • DOI

      10.1007/s12020-020-02298-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between thyroid tumor radiosensitivity and nuclear localization of DNA-dependent protein kinase catalytic subunit2020

    • Author(s)
      Ihara M, Shichijo K, Ashizawa K, Matsuda K, Otsubo R, Horie I, Nakashima M, Kudo T
    • Journal Title

      J Radiat Res

      Volume: 61 Issue: 4 Pages: 511-516

    • DOI

      10.1093/jrr/rraa032

    • NAID

      120006988124

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective effects of a cystine and theanine mixture against acute radiation injury in rats2020

    • Author(s)
      Matsuu-Matsuyama Mutsumi、Shichijo Kazuko、Tsuchiya Takashi、Kondo Hisayoshi、Miura Shiro、Matsuda Katsuya、Sekine Ichiro、Nakashima Masahiro
    • Journal Title

      Environmental Toxicology and Pharmacology

      Volume: 78 Pages: 103395-103395

    • DOI

      10.1016/j.etap.2020.103395

    • NAID

      120006988216

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological and functional changes in neonatally X-irradiated thyroid gland in rats2020

    • Author(s)
      Fujimoto Nariaki、Matsuu-Matsuyama Mutsumi、Nakashima Masahiro
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 2 Pages: 231-240

    • DOI

      10.1507/endocrj.EJ19-0245

    • NAID

      130007802880

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological analysis of papillary thyroid carcinoma detected during ultrasound screening examinations in Fukushima2019

    • Author(s)
      Suzuki Shinichi、Bogdanova Tetiana I.、Saenko Vladimir A.、Hashimoto Yuko、Ito Masahiro、Iwadate Manabu、Rogounovitch Tatiana I.、Tronko Mykola D.、Yamashita Shunichi
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 2 Pages: 817-827

    • DOI

      10.1111/cas.13912

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel diagnostic method for thyroid follicular tumors based on immunofluorescence analysis of p53-binding protein 1 expression: detection of genomic instability2019

    • Author(s)
      Otsubo Ryota、Matsuda Katsuya、Mussazhanova Zhanna、Sato Ayako、Matsumoto Megumi、Yano Hiroshi、Oikawa Masahiro、Kondo Hisayoshi、Ito Masahiro、Miyauchi Akira、Hirokawa Mitsuyoshi、Nagayasu Takeshi、Nakashima Masahiro
    • Journal Title

      Thyroid

      Volume: 印刷中 Issue: 5 Pages: 657-665

    • DOI

      10.1089/thy.2018.0548

    • NAID

      120006987702

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gray Matter Heterotopia: Histological Evidence of Intrauterine Radiation Exposure in a Nagasaki Atomic Bomb Survivor2019

    • Author(s)
      Akazawa Yuko、Ito Masahiro、Naito Shinji、Kishikawa Masao、Sekine Ichiro、Nakashima Masahiro
    • Journal Title

      Radiation Research

      Volume: 192 Issue: 6 Pages: 666-666

    • DOI

      10.1667/rr15390.1

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cribriform-Morular Variant of Papillary Thyroid Carcinoma Shows High Ki-67 Labeling Indices, despite Its Excellent Prognosis2019

    • Author(s)
      Hirokawa Mitsuyoshi、Matsuda Katsuya、Kudo Takumi、Higuchi Miyoko、Suzuki Ayana、Takada Nami、Nakashima Masahiro、Miyauchi Akira
    • Journal Title

      Pathobiology

      Volume: 86 Issue: 5-6 Pages: 248-253

    • DOI

      10.1159/000501097

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice2019

    • Author(s)
      Kurashige Tomomi、Nakajima Yasuyo、Shimamura Mika、Matsuyama Mutsumi、Yamada Masanobu、Nakashima Masahiro、Nagayama Yuji
    • Journal Title

      Endocrinology

      Volume: 160 Issue: 9 Pages: 2085-2092

    • DOI

      10.1210/en.2019-00312

    • NAID

      120006988409

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TERT mRNA Expression as a Novel Prognostic Marker in Papillary Thyroid Carcinomas2019

    • Author(s)
      Tanaka Aya、Matsuse Michiko、Saenko Vladimir、Nakao Tomoe、Yamanouchi Kosho、Sakimura Chika、Yano Hiroshi、Nishihara Eijun、Hirokawa Mitsuyoshi、Suzuki Keiji、Miyauchi Akira、Eguchi Susumu、Yoshiura Ko-ichiro、Yamashita Shunichi、Nagayasu Takeshi、Mitsutake Norisato
    • Journal Title

      Thyroid

      Volume: 29 Issue: 8 Pages: 1105-1114

    • DOI

      10.1089/thy.2018.0695

    • NAID

      120006988431

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The JAK/STAT3 and NF-kappa B signaling pathways regulate cancer stem cell properties in anaplastic thyroid cancer cells2019

    • Author(s)
      K. Shiraiwa, M. Mitsutake, Y. Nakazawa, T. Ogi, K. Suzuki, V. Saenko, K. Umezawa, S. Yamashita, K. Tsukamoto
    • Journal Title

      Thyroid

      Volume: in press Issue: 5 Pages: 674-682

    • DOI

      10.1089/thy.2018.0212

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] チェルノブイリ原発事故後甲状腺がんの病理学的特徴.2020

    • Author(s)
      伊東正博、ボグダノワタチアナ, サエンコウラディミール, 三浦史郎, 中島正洋, 山下俊一
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] CTB病理部会: WHO組織分類第4版(2017年)の甲状腺腫瘍・境界病変の診断基準の改定に伴う問題.2020

    • Author(s)
      伊東正博, 三浦史郎, 三原裕美, 添田李子
    • Organizer
      第74回国立病院総合医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 甲状腺腫瘍における膨大細胞形態とエピジェネティック調節によるMIEAP発現の損失の関連性2020

    • Author(s)
      ムサジャノワ・ジャンナ, 嶋村 美加, 黒濱 大和, 伊東 正博, 山下 弘幸, 中島 正洋, 永山 雄二
    • Organizer
      日本内分泌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 福島における超音波スクリーニングによって発見された甲状腺乳頭癌の病理組織学的検討2019

    • Author(s)
      鈴木 眞一, 岩舘 学, Bogdanova Tetiana, Saenko Vladimr A., 橋本 優子, 伊東 正博, Rogounovitch Tatiana I., 鈴木 聡, 松本 佳子, 山下 俊一
    • Organizer
      日本内分泌外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 福島県における甲状腺検診の現況、課題と今後 福島甲状腺検査で発見された小児甲状腺癌症例の病理組織学的特徴2019

    • Author(s)
      長沼 廣, 廣川 満良, 伊東 正博, 坂本 穆彦, 橋本 優子
    • Organizer
      日本内分泌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] チェルノブイリ組織バンク 19年間の活動状況と課題2019

    • Author(s)
      伊東 正博, Bogdanova Tetiana, Dvinskykh Niena, Fadda Guido, Hunt Geniffer, Thomas Gerry, 中島 正洋, 山下 俊一
    • Organizer
      日本病理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 甲状腺に原発した成人T細胞白血病・リンパ腫2019

    • Author(s)
      本多 明日美, 牧山 純也, 藤岡 真知子, 千綿 雅彦, 中島 潤, 三好 寛明, 今泉 芳孝, 伊東 正博, 大島 孝一, 吉田 真一郎
    • Organizer
      日本リンパ網内系学会
    • Related Report
      2019 Research-status Report
  • [Presentation] チェルノブイリ組織バンクの活動状況 -課題と診断基準の改定に伴う問題-2019

    • Author(s)
      伊東正博、三浦史郎, 三原裕美, 中島正洋, 山下俊一
    • Organizer
      日本甲状腺病理学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Association between oncocytic morphology of thyroid tumors and loss of MIEAP expression through epigenetic regulation2019

    • Author(s)
      Zhanna Mussazhanova, Mika Shimamura, Hirokazu Kurohama, Masahiro Ito, Hiroyuki Yamashita, Masahiro Nakashima, Yuji Nagayama
    • Organizer
      日本甲状腺病理学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 甲状腺細胞診報告様式ベセスダシステム 第2版 (日本語)2019

    • Author(s)
      伊東正博、坂本 穆彦 (監修, 翻訳)
    • Total Pages
      248
    • Publisher
      丸善書店
    • Related Report
      2019 Research-status Report
  • [Remarks] Chernobyl Tissue Bank

    • URL

      https://www.chernobyltissuebank.com/documents

    • Related Report
      2021 Annual Research Report
  • [Remarks] Chernobyl Tissue Bank

    • URL

      https://www.chernobyltissuebank.com/bibliography.htm

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-03-16  

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