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2019 年度 実施状況報告書

Genome-wide gene-environmental interaction analysis of exposures to radiation and nitrates as modifiers of the risk for thyroid cancer in the Chernobyl region

研究課題

研究課題/領域番号 19KK0267
研究機関長崎大学

研究代表者

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)

研究分担者 横田 賢一  長崎大学, 原爆後障害医療研究所, 助教 (90754622)
ログノビッチ タチアナ  長崎大学, 原爆後障害医療研究所, 客員研究員 (30423643)
中山 貴文  長崎大学, 原爆後障害医療研究所, 助教 (80829440)
研究期間 (年度) 2019-10-07 – 2023-03-31
キーワードChernobyl / thyroid cancer / radiation / environmental factors
研究実績の概要

Genetic and environmental factors are thought to contribute to the risk of development of thyroid cancer. The purpose of this study is to analytically measure on the whole-genome scale the impact of interactions of individual genetic variants (G) with environmental factors (E) such as radiation, iodine and nitrates (thus, GxE interactions) on the risk for thyroid malignancy, using the Chernobyl region as a paradigm of radiation-associated thyroid carcinogenesis.
Our previous whole-genome study of genetic predisposition to radiation-related thyroid carcinogenesis was performed in the groups of patients with thyroid cancer developed after the Chernobyl accident and healthy control individuals from Belarus. In the course of this study, data on radiation thyroid dose, iodine level in soil and nitrate concentration in drinking water in the place of residence of study participants will be generated and integrated with the available genomic data in comprehensive statistical and machine learning models.
This study is an international interdisciplinary collaborative research to be conducted by the specialists in different areas of knowledge such as genome analysis, medical oncology and pathology, environmental factor effects, and physical and mathematical radiation dosimetry. Knowledge from GxE interactions is expected to provide essential data for scientific evidence-based risk communications and individual risk management under the conditions of increasing medical exposures worldwide, and accidental radiation exposure or technogenic radiation disaster.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

During this year’s research period, the workflow was focused on i) collecting and obtaining the detailed clinicopathological information on the participants of the study who developed thyroid cancer after the Chernobyl accident at childhood age, and ii) reconstruction of individual thyroid radiation doses for childhood thyroid cancer patients and healthy controls in the study.
Clinicopathological data were collected and reviewed through the international collaboration with Minsk City Oncology Dispensary. Information on about 400 (of 1004) was refined and entered to an electronic spreadsheet.
A kick-off meeting on radiation dosimetry was held to determine the strategy of dosimetric works. To prepare data for radiation dose reconstruction, the information on the place of residence at a moment of exposure was prepared on all 1049 control subjects in the study and entered to an MS Access database through the collaboration with the dosimetric team in Minsk, Belarus managed by a scientific supervisor from the National Institute of Health, NIH, USA.

今後の研究の推進方策

We plan to continue obtaining and reviewing clinicopathological information on Chernobyl childhood thyroid cancer in cooperation with Minsk City Oncologic Dispensary, Belarus. It is expected that information on about 600 thyroid cancer cases will be collected and entered to an electronic spreadsheet suitable for statistical calculations.
To reconstruct individualized radiation thyroid doses, we will continue collection of information on existing radiation contamination data, and age-, gender- and type of residence-specific consumption of locally produced foods, and thyroid activity measurements data whenever available for approximately 500 patients with Chernobyl thyroid cancer in Belarus. This work will be done in collaboration with the dosimetric team in Minsk, Belarus under the scientific oversight from the National Institute of Health, NIH, USA.

次年度使用額が生じた理由

The fund-consuming parts of the study during the last year included holding the dosimetric kick-off meeting (travel), remuneration for overseas assist and purchase of items required for future field work and data storage. Since funding was available from 2019 October, we could not use up allocated funds and shifted the remainder to FY 2020.
The aggregated FY2020 funds will be nearly completely used for the field work in Belarus (when travel restrictions are lifted) and remuneration for overseas assist. Major focus will be on collecting, processing and storing the information on clinicopathological characteristics and information required for individual dose reconstruction for radiation-related Chernobyl thyroid cancer cases.

  • 研究成果

    (19件)

すべて 2019 その他

すべて 国際共同研究 (3件) 雑誌論文 (6件) (うち国際共著 6件、 査読あり 6件、 オープンアクセス 1件) 学会発表 (8件) (うち国際学会 1件、 招待講演 4件) 図書 (1件) 備考 (1件)

  • [国際共同研究] Minsk City Oncologic Dispensary/Institute for Nature Management(ベラルーシ)

    • 国名
      ベラルーシ
    • 外国機関名
      Minsk City Oncologic Dispensary/Institute for Nature Management
  • [国際共同研究] National Institutes of Health, NIH/NCI(米国)

    • 国名
      米国
    • 外国機関名
      National Institutes of Health, NIH/NCI
  • [国際共同研究] IARC(フランス)

    • 国名
      フランス
    • 外国機関名
      IARC
  • [雑誌論文] Histopathological analysis of papillary thyroid carcinoma detected during ultrasound screening examinations in Fukushima2019

    • 著者名/発表者名
      Suzuki S, Bogdanova TI, Saenko VA, Hashimoto Y, Ito M, Iwadate M, Rogounovitch TI, Tronko MD, Yamashita S.
    • 雑誌名

      Cancer Sci

      巻: 110 ページ: 817-827

    • DOI

      10.1111/cas.13912.

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Childhood leukemia in Ukraine after the Chornobyl accident.2019

    • 著者名/発表者名
      Liubarets TF, Shibata Y, Saenko VA, Bebeshko VG, Prysyazhnyuk AE, Bruslova KM, Fuzik MM, Yamashita S, Bazyka DA.
    • 雑誌名

      Radiat Environ Biophys

      巻: 58 ページ: 553-562

    • DOI

      10.1007/s00411-019-00810-4.

    • 査読あり / 国際共著
  • [雑誌論文] The JAK/STAT3 and NF-κB signaling pathways regulate cancer stem cell properties in anaplastic thyroid cancer cells.2019

    • 著者名/発表者名
      Shiraiwa K, Matsuse M, Nakazawa Yu, Ogi T, Suzuki K, Saenko V, Xu S, Umezawa K, Yamashita S, Tsukamoto K, Mitsutake N.
    • 雑誌名

      Thyroid

      巻: 29 ページ: 674-682

    • DOI

      10.1089/thy.2018.0212.

    • 査読あり / 国際共著
  • [雑誌論文] TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131I uptake in metastases.2019

    • 著者名/発表者名
      Meng Z, Matsuse M, Saenko V, Yamashita S, Ren P, Zheng X, Jia Q, Tan J, Li N, Zheng W, Zhao L, Mitsutake N.
    • 雑誌名

      IUBMB Life

      巻: 71 ページ: 1030-1040

    • DOI

      10.1002/iub.2056.

    • 査読あり / 国際共著
  • [雑誌論文] TERT mRNA expression as a novel prognostic marker in papillary thyroid carcinomas.2019

    • 著者名/発表者名
      Tanaka A, Matsuse M, Saenko V, Nakao T, Yamanouchi K, Sakimura C, Yano H, Nishihara E, Hirokawa M, Suzuki K, Miyauchi A, Eguchi S, Yoshiura KI, Yamashita S, Nagayasu T, Mitsutake N.
    • 雑誌名

      Thyroid

      巻: 29 ページ: 1105-1114

    • DOI

      10.1089/thy.2018.0695.

    • 査読あり / 国際共著
  • [雑誌論文] Radiation-Induced Thyroid Cancers: Overview of Molecular Signatures.2019

    • 著者名/発表者名
      Suzuki K, Saenko V, Yamashita S, Mitsutake N.
    • 雑誌名

      Cancers (Basel)

      巻: 11 ページ: 1-12

    • DOI

      10.3390/ cancers11091290.

    • 査読あり / 国際共著
  • [学会発表] Genetic alterations in thyroid cancers in Fukushima2019

    • 著者名/発表者名
      N.Mitsutake, M.Matsuse, V.Saenko, S.Suzuki, S.Yamashita
    • 学会等名
      The 3rd Joint Symposium between Nagasaki University and Wurzburg University
    • 国際学会 / 招待講演
  • [学会発表] Genetic alterations in young thyroid cancer cases in Fukushima2019

    • 著者名/発表者名
      光武範吏、岩館学、松瀬美智子、Vladimir Saenko、鈴木眞一、山下俊一
    • 学会等名
      第92回 日本内分泌学会学術総会
    • 招待講演
  • [学会発表] Assessment of 4 genetic loci conferring risk for thyroid cancer with regard to patient’s age and tumor etiology2019

    • 著者名/発表者名
      Rogounovitch TI, Mitsutake N, Leonava TA, Drozd VM, Takahashi M, Matsuda F, Yamashita S, Saenko VA
    • 学会等名
      第92回 日本内分泌学会学術総会
  • [学会発表] Childhood thyroid cancer in Chernobyl: implications for Fukushima2019

    • 著者名/発表者名
      VA Saenko
    • 学会等名
      第43回日本乳腺甲状腺超音波医学会学術集会
    • 招待講演
  • [学会発表] Thyroid cancer and sonographical findings after the Chernobyl nuclear power plant accident2019

    • 著者名/発表者名
      VM Drozd, VA Saenko,TI Rogounovitch, SYamashita, I Branovan, C.Reiners
    • 学会等名
      第43回日本乳腺甲状腺超音波医学会学術集会
    • 招待講演
  • [学会発表] BRAF mutation elevates the chance of recurrence of papillary thyroid carcinoma in patients from Russia2019

    • 著者名/発表者名
      V Saenko, T Rogounovitch, A Abrosimov, A Sidorin, P Rumyantsev, N Mitsutake, S Yamashita
    • 学会等名
      第62回 日本甲状腺学会学術集会
  • [学会発表] Difference between BRAFV600E mutated post-Chernobyl and sporadic young adult PTCs from Belarus2019

    • 著者名/発表者名
      T Rogounovitch, M Frydman, S Mankovskaya, N Mitsutake, S Yamashita, V Saenko
    • 学会等名
      第62回 日本甲状腺学会学術集会
  • [学会発表] 甲状腺乳頭癌における TERTプロモーター領域のメチル化とmRNA発現の検討2019

    • 著者名/発表者名
      松瀬美智子、田中彩、三嶋博之、吉浦孝一郎、 Vladimir Saenko、鈴木啓司、光武範吏
    • 学会等名
      第62回 日本甲状腺学会学術集会
  • [図書] Thyroid FNA Cytology. Differential Diagnoses and Pitfalls. 2nd Ed.2019

    • 著者名/発表者名
      TI Bogdanova, VA Saenko, LYu Zurnadzhy, TI Rogounovitch, M Ito, SV Chernyshov, GA Thomas, MD Tronko, S Yamashita.
    • 総ページ数
      549-563
    • 出版者
      Springer Nature Singapore Pte Ltd.
    • ISBN
      978-981-13-1896-2
  • [備考] Department of Radiation Molecular Epidemiology

    • URL

      https://www-sdc.med.nagasaki-u.ac.jp/dhrc/index.html

URL: 

公開日: 2021-01-27  

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