Genome-wide gene-environmental interaction analysis of exposures to radiation and nitrates as modifiers of the risk for thyroid cancer in the Chernobyl region

2022 Fiscal Year Research-status Report

• Project/Area Number: 19KK0267
• Research Institution: Nagasaki University
• 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)
• 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)
• Project Period (FY): 2019-10-07 – 2024-03-31
• Keywords: Chernobyl / thyroid cancer / radiation / environmental factors / GxE interaction

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 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.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

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.

Strategy for Future Research Activity

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).

Causes of Carryover

The unspent portion of the budget was transferred to the next fiscal year because the international travel to Belarus was prohibited during the coronavirus pandemic and then due to the political situation around the ongoing armed conflict in vicinity to the country.
The consolidated planned and transferred portions of the budget will be used to cover the cost of genotyping the validation set of samples (~300 cases and controls), and purchase of items required for data storage and data analysis.
Data storage and backup will require the purchase of additional 12-16TB external network-attached storage (NAS) device. We also plan to purchase an annual license for several software packages, all to be used in Nagasaki University.
Only domestic travel is considered at a moment, no overseas duty trips during this year are planned.

Research Products

• [Int'l Joint Research] Minsk City Oncologic Dispensary/Institute for Nature Management(ベラルーシ)
  • Country Name: BELARUS
  • Counterpart Institution: Minsk City Oncologic Dispensary/Institute for Nature Management
• [Int'l Joint Research] National Institutes of Health, NIH/NCI(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: National Institutes of Health, NIH/NCI
• [Int'l Joint Research] IARC(フランス)
  • Country Name: FRANCE
  • Counterpart Institution: IARC
• [Journal Article] The relationship of the clinicopathological characteristics and treatment results of post-Chornobyl papillary thyroid microcarcinomas with the latency period and radiation exposure (2022)
  • Author(s): Bogdanova T, Chernyshov S, Zurnadzhy L, Rogounovitch TI, Mitsutake N, Tronko M, Ito M, Bolgov M, Masiuk S, Yamashita S, Saenko VA
  • Journal Title: Front Endocrinol (Lausanne) Volume: 3 Pages: 1078258
  • DOI: 10.3389/fendo.2022.1078258.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The high degree of similarity in histopathological and clinical characteristics between radiogenic and sporadic papillary thyroid microcarcinomas in young patients (2022)
  • Author(s): Bogdanova T, Chernyshov S, Zurnadzhy L, Rogounovitch TI, Mitsutake N, Tronko M, Ito M, Bolgov M, Masiuk S, Yamashita S, Saenko VA
  • Journal Title: Front Endocrinol (Lausanne) Volume: 13 Pages: 970682
  • DOI: 10.3389/fendo.2022.970682.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological Implications of the BRAFV600E Mutation in Papillary Thyroid Carcinoma of Ukrainian Patients Exposed to the Chernobyl Radiation in Childhood: A Study for 30 Years After the Accident (2022)
  • Author(s): Zurnadzhy L, Bogdanova T, Rogounovitch TI, Ito M, Tronko M, Yamashita S, Mitsutake N, Bolgov M, Chernyshov S, Masiuk S, Saenko VA
  • Journal Title: Front Med (Lausanne) Volume: 9 Pages: 882727
  • DOI: 10.3389/fmed.2022.882727.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Remarks] Department of Radiation Molecular Epidemiology
  • URL: https://www-sdc.med.nagasaki-u.ac.jp/dhrc/index.html