2021 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 / GxE interactions |
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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 (hence, 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 taking into account only demographic information.
In the course of the present study, data on individual radiation thyroid dose, and iodine level in soil and nitrate concentration in drinking water in the place of residence of study participants are being generated and integrated with genomic data in comprehensive statistical and machine learning models.
This study is an international interdisciplinary collaborative research conducted by the specialists in different areas of knowledge such as genome analysis, medical oncology and pathology, environment, and physical 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) verification of clinicopathological information on the participants of the study who developed thyroid cancer after exposure to Chernobyl radiation 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 150 cases was refined and entered to an electronic spreadsheet. Cumulatively, verified clinicopathological data is available for >90% thyroid cancer cases in 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 were developed 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 and used as an input to reconstruct individual radiation thyroid doses for 2041 individuals (publication #2). This was a 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 thyroid cancer cases in cooperation with Minsk City Oncologic Dispensary, Belarus. It is expected that data on about 50 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.
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 will be prepared in collaboration with the Institute for Nature Management, Minsk, Belarus.
With the information on individual radiation doses, demography and clinicopathological characteristics, we plan to develop statistical models addressing the following questions: 1) genetics*clinicopathological tumor characteristics among the tumors; 2) radiation thyroid dose* clinicopathological tumor characteristics among the tumors; 3) genetics*radiation thyroid dose* clinicopathological tumor characteristics among the tumors; 4) genetics*radiation thyroid dose* thyroid cancer in case-control setting, and 5) genetics*radiation thyroid dose* thyroid cancer in time to disease setting (survival models).
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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 environmental nitrate and iodine concentrations (if possible), and purchase of items required for data storage and data analysis.
The aggregated FY2022 funds will be used for remuneration of overseas environmental data collection (if possible). Data storage and backup will require the purchase of additional 12-16TB external/LAN HDD. We also plan to purchase annual licenses for Stata 17 software packages, all to be used in Nagasaki University.
If situation with coronavirus epidemic improves as well as other previously unforeseeable circumstances resolve, and travel restrictions are lifted, we will hold a research progress meeting on environmental data at the time of the Chernobyl accident in Minsk, Belarus, and dispatch a co-investigator from Nagasaki University to Minsk City Oncologic Dispensary to review clinicopathological data.
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Research Products
(9 results)
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[Journal Article] Thyroid dose estimates for the genome-wide association study of thyroid cancer in persons exposed in Belarus to 131I after the Chernobyl accident.2021
Author(s)
Drozdovitch V, Minenko V, Kukhta T, Viarenich K, Trofimik S, Rogounovitch T, Nakayama T, Drozd V, Veyalkin I, Mitsutake N, Ostroumova E, Saenko V.
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Journal Title
J Radiat Res.
Volume: 62(6)
Pages: 982-998
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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