| 研究課題/領域番号 |
19KK0267
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| 研究種目 |
国際共同研究加速基金(国際共同研究強化(B))
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| 配分区分 | 基金 |
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| 審査区分 |
中区分63:環境解析評価およびその関連分野
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| 研究機関 | 長崎大学 |
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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)
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| 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, 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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| 研究期間 (年度) |
2019-10-07 – 2024-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
18,460千円 (直接経費: 14,200千円、間接経費: 4,260千円)
2022年度: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2021年度: 5,460千円 (直接経費: 4,200千円、間接経費: 1,260千円)
2020年度: 3,900千円 (直接経費: 3,000千円、間接経費: 900千円)
2019年度: 4,420千円 (直接経費: 3,400千円、間接経費: 1,020千円)
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| キーワード | Chernobyl / thyroid cancer / radiation / environmental factors / GxE interaction / GxE interactions |
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| 研究開始時の研究の概要 |
To elucidate the role of gene-environmental interactions in carcinogenesis, data on radiation thyroid dose, and the iodine level in soil and nitrate concentration in drinking water will be integrated with the whole-genome data for the group of patients and healthy control persons exposed to Chernobyl radiation. This study is an international interdisciplinary research aimed at the analysis of the impact of each potential risk factor and of their joint effect on thyroid carcinogenesis after radiation exposure at the individual level.
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| 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 (hence, GxE interactions) on the risk for thyroid malignancy in the Chernobyl-affected region.
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, i.e. using an ecological design.
In 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 at the time of exposure are being generated and integrated with the available 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 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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
During this year, the workflow was focused on i) the update of follow-up information on the radiation-exposed participants of the study with thyroid cancer, ii) clarification of reconstructed individual thyroid radiation doses for cases with updated residence information in April-June 1986, and iii) collecting the information on soil iodine and nitrate in drinking water at the place of residence in April-June 1986 for all participants of the study.
Clinicopathological and follow-up data were collected through the international collaboration with Minsk City Oncology Dispensary. Cumulatively, verified information is available for ~95% thyroid cancer cases in the study.
Individual or individualized radiation thyroid doses were reconstructed for all study participants using a computation algorithm that considered the residential/relocation history, consumption rates of locally produced cow milk, dairy products, and leafy vegetables. 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.
Obtaining the information on soil iodine and nitrate level in drinking water in April-June 1986 is somewhat delaying because of the coronavirus pandemic and the armed conflict between Russia and Ukraine due to which visiting Belarus and the direct information exchange were suspended. Currently, we are collecting the desired data using geolocation coordinates of the places of living of all participants of the study and retrospective information on the environment monitoring in Belarus.
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| 今後の研究の推進方策 |
We plan to supplement the thyroid dosimetry data with an additional parameter, the Probability of cancer causation due to radiation using software available from NIH. POC will be calculated using the information on each patient’s gender, birth year, diagnosis year, radiation dose from I-131 for the thyroid cancer scenario. These data will be 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, probability of cancer causation due to radiation, demographic and clinicopathological characteristics, we plan to test the impact of the genetic factors in the following statistical models: 1) genetics*clinicopathological tumor characteristics case-only; 2) radiation thyroid dose* clinicopathological tumor characteristics case-only; 3) genetics*radiation thyroid dose* clinicopathological tumor characteristics case-only; 4) genetics*radiation thyroid dose* thyroid cancer in case-control setting, and 5) genetics*radiation thyroid dose* thyroid cancer in time to disease in case-only and case-control settings (survival models).
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