2019 Fiscal Year Research-status Report
Genome-wide gene-environmental interaction analysis of exposures to radiation and nitrates as modifiers of the risk for thyroid cancer in the Chernobyl region
| Project/Area Number |
19KK0267
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| Research Institution | Nagasaki University |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
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)
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| Project Period (FY) |
2019-10-07 – 2023-03-31
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| Keywords | Chernobyl / thyroid cancer / radiation / environmental factors |
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| Outline of Annual Research Achievements |
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.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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.
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| Strategy for Future Research Activity |
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.
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| Causes of Carryover |
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.
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[Journal Article] The JAK/STAT3 and NF-κB signaling pathways regulate cancer stem cell properties in anaplastic thyroid cancer cells.2019
Author(s)
Shiraiwa K, Matsuse M, Nakazawa Yu, Ogi T, Suzuki K, Saenko V, Xu S, Umezawa K, Yamashita S, Tsukamoto K, Mitsutake N.
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Journal Title
Thyroid
Volume: 29
Pages: 674-682
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131I uptake in metastases.2019
Author(s)
Meng Z, Matsuse M, Saenko V, Yamashita S, Ren P, Zheng X, Jia Q, Tan J, Li N, Zheng W, Zhao L, Mitsutake N.
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Journal Title
IUBMB Life
Volume: 71
Pages: 1030-1040
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] TERT mRNA expression as a novel prognostic marker in papillary thyroid carcinomas.2019
Author(s)
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.
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Journal Title
Thyroid
Volume: 29
Pages: 1105-1114
DOI
Peer Reviewed / Int'l Joint Research
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