2020 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, 特任研究員 (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 550 was refined and entered to an electronic spreadsheet. Cumulatively, clinicopathological data is available for 920 (>90%) participants of the study.
For thyroid dosimetry, all study participants were subdivided into 4 groups with regard to the type of information available: a) thyroid radioactivity measurement and interview; b) measurement/no interview; c) no measurement/interview; and d) no measurement/no interview. Individual thyroid dose computation algorithms are under development for each group, considering the residential/relocation history, consumption rates of locally produced cow milk, dairy products, and leafy vegetables. These data along with 131I ground deposition levels in the settlements of residence of the study participants were entered to an MS Access database through the collaboration with the dosimetric team in Minsk, Belarus managed by a scientific supervisor from the National Institutes of Health, NIH/NCI, USA.
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| Strategy for Future Research Activity |
We plan to finish obtaining and reviewing clinicopathological information on Chernobyl childhood thyroid cancer in cooperation with Minsk City Oncologic Dispensary, Belarus. It is expected that data on about 100 remaining thyroid cancer cases from patients treated in several third-party medical institutions in Belarus will be collected and entered to an electronic spreadsheet suitable for statistical calculations.
To reconstruct individualized radiation thyroid doses, we will accomplish the development of computation algorithms for different groups of study participants, and finalize the database on all study participants. The database will be used to produce an input file for calculation of individual thyroid doses, including estimates of the reconstructed dose reliability. It is expected that during this year the individual dose estimates will be obtained for each study participant. 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/NCI, USA.
We will start preparing a database on nitrate in drinking water and soil iodine concentrations at the places of residence at the time of the Chernobyl accident for all study participants in collaboration with the Institute for Nature Management, Minsk, Belarus.
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| Causes of Carryover |
The fund-consuming parts of the study for this fiscal year include the support of overseas assistants on thyroid clinicopathology and dosimetry research, purchase of items required for data storage and data analysis.
The aggregated FY2021 funds will be used for remuneration of overseas clinicopathological data management and thyroid dosimetry accomplishment. Data storage and backup will require the purchase of a 12-16TB external/LAN HDD. We also plan to purchase annual licenses for JMP Genomics 9.1 and Stata 17 software packages.
If situation with coronavirus epidemic improves and travel restrictions are lifted, we will hold a research progress meeting on thyroid dosimetry in Minsk, Belarus, and dispatch a co-investigator from Nagasaki University to Minsk City Oncologic Dispensary to review clinicopathological data.
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[Journal Article] The Contribution of Genetic Variants to the Risk of Papillary Thyroid Carcinoma in the Kazakh Population: Study of Common Single Nucleotide Polymorphisms and Their Clinicopathological Correlations2021
Author(s)
Mussazhanova Z, Rogounovitch TI, Saenko VA, Krykpayeva A, Espenbetova M, Azizov B, Kondo H, Matsuda K, Kalmatayeva Z, Issayeva R, Yeleubayeva Z, Madiyeva M, Mukanova A, Sandybayev M, Bolsynbekova S, Kozykenova Z, Yamashita S, Nakashima M.
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Journal Title
Front Endocrinol (Lausanne)
Volume: 11
Pages: 1-10
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Papillary Thyroid Carcinoma in Ukraine After Chernobyl and in Japan After Fukushima: Different Histopathological Scenarios2020
Author(s)
Bogdanova TI, Saenko VA, Hashimoto Y, Hirokawa M, Zurnadzhy LY, Hayashi T, Ito M, Iwadate M, Mitsutake N, Rogounovitch TI, Sakamoto A, Naganuma H, Miyauchi A, Tronko MD, Thomas G, Yamashita S, Suzuki S.
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Journal Title
Thyroid
Volume: 4
Pages: 1-13
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Predictors of the efficacy of radioiodine therapy of Graves' disease in children and adolescents2020
Author(s)
Rumyantsev PO, Saenko VA, Dzeytova DS, Trukhin AA, Sheremeta MS, Slashchuk KY, Degtyarev MV, Serzhenko SS, Yasuchenia VS, Zakharova SM, Sirota YI.
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Journal Title
Probl Endokrinol (Mosk)
Volume: 66
Pages: 68-76
DOI
Peer Reviewed
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[Presentation] Different pathological scenarios of thyroid cancer in Chernobyl and Fukushima2020
Author(s)
V Saenko, T Bogdanova, Y Hashimoto, M Hirokawa, L Zurnadzhy, T Hayashi, M Ito, M Iwadate, N Mitsutake, T Rogounovitch, A Sakamoto, H Naganuma, A Miyauchi, M Tronko, G Thomas, S Yamashita, S Suzuki
Organizer
第63回日本放射線影響学会
Invited
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