Comprehensive Genomic Characterization of Radiation-Related Thyroid Cancer in Ukraine
A major health effect of the 1986 Chernobyl nuclear power plant accident is the increase in incidence of thyroid cancer, particularly among those exposed to radioactive fallout as children or adolescents. Studies of the population of children or adolescents exposed to radioactive fallout have been carried out by REB and the Institute of Endocrinology and Metabolism (IEM) in Ukraine. They have found a strong, linear relationship between individual I-131 thyroid dose and risk of thyroid cancer that remains elevated two decades after exposure (Brenner et al., 2011). The investigators estimate that half of the incident cancers in the cohort could be attributed to I-131 exposure. A parallel study in Belarus found a similarly strong association for prevalent thyroid cancers (Zablotska et al., 2011).
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Background & Purpose
Chernobyl Accident: Radiation and Health Effects
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To date, the molecular mechanisms underlying the association between I-131 exposure and thryoid cancer risk remain poorly understood. Jointly with colleagues at IEM, Bundeswehr Institute of Radiobiology, and the University of Pittsburgh, investigators in REB conducted preliminary studies of mRNA expression and targeted somatic alterations using DNA and RNA aliquots extracted from tumor/normal pairs drawn from 62 Ukrainian cases received through the Chernobyl Tissue Bank (CTB) (Abend et al., 2012; Abend et al., 2013; Leeman-Neill et al., 2013; Leeman-Neill et al., 2014).
We then substantially expanded this research by conducting a large-scale study to comprehensively characterize the genomic alterations in thyroid cancers occurring after the Chernobyl accident, partnering with our colleagues at IEM and the CTB. This ongoing study leverages the collection of biological samples (tumor tissue, non-tumor thyroid tissue, blood) with detailed information on radiation exposure from I-131 and clinical and demographic characteristics. The study is generating a rich data resource with assessment of genomic, transcriptomic, and epigenomic patterns to provide insights into radiation-induced carcinogenesis and the development of thyroid cancer more generally.
For more information, contact Lindsay Morton.
Select Findings & Publications
The first major analysis (Morton et al., 2021) from this data resource demonstrated a dose-dependent carcinogenic effect of radiation derived primarily from DNA double-strand breaks repaired by non-homologous end-joining that initiate subsequent thyroid tumor growth, the patterns of which are shaped not by radiation exposure but rather by the specific driver gene. Ongoing analyses further explore radiation-related carcinogenesis, metastatic disease, and effects of age.
Brenner AV, Tronko MD, Hatch M, et al. I-131 dose-response for incident thyroid cancers related to the Chornobyl accident in Ukraine. Environ Health Perspect 2011
Zablotska LB, Ron E, Rozhko AV, et al. Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident. BJC 2011
Abend M, Pfeiffer RM, Ruf C, et al. Dose dependent gene expression in thyroid cancer and corresponding normal tissue following the Chernobyl accident. PloS One 2012
Abend M, Pfeiffer RM, Ruf C, et al. Iodine-131 dose-dependent gene expression: Alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers. Br J Cancer 2013
Morton LM, Karyadi DM, Stewart C, et al. Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident. Science 2021