| 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, 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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| 研究期間 (年度) |
2019-10-07 – 2025-03-31
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| 研究課題ステータス |
交付 (2023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 / gene-environment / 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, hence GxE interactions) such as radiation, iodine and nitrates on the risk for thyroid malignancy, using the Chernobyl region as a paradigm of radiation-associated thyroid carcinogenesis.
Our previous genome-wide association study of radiation-related thyroid cancer was performed in the groups of thyroid cancer patients and healthy control individuals from in an ecological design setting.
In the course of the present study, data on individual radiation thyroid dose, iodine level in soil and nitrate concentration in drinking water in the place of residence of study participants at the time of the Chernobyl accident are 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 physical and mathematical radiation dosimetry. Knowledge from GxE interactions is expected to provide data for scientific evidence-based risk communications and individual risk management under the conditions of increasing medical exposures worldwide, 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 fiscal year’s research period, all individual/individualized data on environmental exposures (i.e., reconstructed individual thyroid radiation doses, and soil iodine and nitrate levels in drinking water at the place of residence in April-June 1986) of the study participants were finalized, cleaned-up and formalized along with clinicopathological information on patients who had developed thyroid cancer.
Radiation thyroid doses were reconstructed through the collaboration with the dosimetric team in Minsk, Belarus managed by a scientific supervisor from the National Institutes of Health, NIH/NCI, USA, and with the contribution from the International Agency for Research on Cancer (IARC/WHO), France.
Despite the difficult international situation due to coronavirus pandemic and an ongoing armed conflict between Russia and Ukraine, due to which visiting Belarus was not possible, information on soil iodine and nitrate levels in drinking water was collected using geolocation coordinates of the places of living of all participants of the study and retrospective information on the environment monitoring in the country.
Clinicopathological and follow-up data were refined through the international collaboration with Minsk City Oncology Dispensary.
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| 今後の研究の推進方策 |
Using the information on individual/individualized radiation doses and environmental exposures to iodine and nitrates, 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) radiation thyroid dose* nitrate*clinicopathological tumor characteristics case-only; 4) radiation thyroid dose* nitrate*soil iodine*clinicopathological tumor characteristics case-only; 5) genetics*radiation thyroid dose* nitrate*soil iodine* clinicopathological tumor characteristics case-only; 6) genetics*radiation thyroid dose*nitrate*soil iodine*thyroid cancer in case-control setting, and 7) genetics*radiation thyroid dose* nitrate*soil iodine*thyroid cancer in time to disease in case-only and case-control settings (survival models). The top-significant SNPs discovered in the previous genome-wide studies will be tested first to evaluate statistical model adequacy and performance. If deemed necessary, additional genotyping will be performed in selected samples.
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