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Integration of a radiation biomarker into modeling of thyroid carcinogenesis and post-Chernobyl risk assessment

In this study a molecular radiation marker has been used for the first time to estimate radiation risks in epidemiological studies.

Ionising radiation induces traceable molecular damage. According to prevailing opinion the development of a disease is not radiation-specific and cannot be distinguished from pathogenesis induced by other co-factors. However, our study provides indication that overexpression of the CLIP2 gene is related to radiation-related progression of thyroid cancer to which a radiation risk can be assigned. To date, such risks could only be determined in extensive radio-epidemiological studies.

Earlier studies of the Research Unit Radiation Cytology have demonstrated that overexpression of the CLIP2 gene can be considered as a radiation marker in cancer tissue of very young patients operated below age 20 yr. With mathematical models of carcinogenesis it could now be shown, that the probability of the occurrence for the radiation marker is related to a dose response, which directly corresponds to the radiation risk in the cohort of Ukrainian Chernobyl children.

In retrospective analysis a reliable radiation marker such as CLIP overexpression can be used to ascertain the radiogenic origin of a disease. This knowledge is of significance for the assessment of late health effects after nuclear accidents and after diagnostic or therapeutic radiation exposure.

The extent of late effects from radiation exposure of children and adolescents, especially the increased incidence of thyroid cancer after the accidents of Chernobyl and Fukushima, could be determined much more accurately with a biological radiation marker compared to statistical analysis of associations in radio-epidemiologicy which constitute the hitherto existing state-of-the-art.

A comprehensive characterisation of the role of CLIP2 as a driver gene in radiation-induced development of thyroid cancer is still lacking. For a final answer adequate cell culture models are necessary to assess the oncogenic potential of CLIP2. Furthermore, the application of the developed model of carcinogenesis to other radio-epidemiological cohorts will provide further insight, if the observed effects are of general nature.

Mechanistic model of radiation-induced thyroid cancer.