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Kaiser, J.C. ; Meckbach, R.* ; Eidemüller, M. ; Selmansberger, M. ; Unger, K. ; Shpak, V.* ; Blettner, M.* ; Zitzelsberger, H. ; Jacob, P.*

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

Carcinogenesis 37, 1152-1160 (2016)
Publ. Version/Full Text Postprint Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Strong evidence for the statistical association between radiation exposure and disease has been produced for thyroid cancer by epidemiological studies after the Chernobyl accident. However limitations of the epidemiological approach in order to explore health risks especially at low doses of radiation appear obvious. Statistical fluctuations due to small case numbers dominate the uncertainty of risk estimates. Molecular radiation markers have been searched extensively to separate radiation- induced cancer cases from sporadic cases. The overexpression of the CLIP2 gene is the most promising of these markers. It was found in the majority of papillary thyroid cancers (PTCs) from young patients included in the Chernobyl tissue bank. Motivated by the CLIP2 findings we propose a mechanistic model which describes PTC development as a sequence of rate-limiting events in two distinct paths of CLIP2-associated and multi-stage carcinogenesis. It integrates molecular measurements of the dichotomous CLIP2 marker from 141 patients into the epidemiological risk analysis for about 13,000 subjects from the Ukrainian-American cohort which were exposed below age 19 yr and were put under enhanced medical surveillance since 1998. For the first time a radiation risk has been estimated solely from marker measurements. Cross checking with epidemiological estimates and model validation suggests that CLIP2 is a marker of high precision. CLIP2 leaves an imprint in the epidemiological incidence data which is typical for a driver gene. With the mechanistic model we explore the impact of radiation on the molecular landscape of PTC. The model constitutes a unique interface between molecular biology and radiation epidemiology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Atomic-bomb Survivors; Cancer-risk; Genomic Instability; External Radiation; Pooled Analysis; Exposure; Ukraine; Carcinoma; Accident; Ret/ptc
ISSN (print) / ISBN 0143-3334
e-ISSN 1460-2180
Journal Carcinogenesis
Quellenangaben Volume: 37, Issue: 12, Pages: 1152-1160 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Reviewing status Peer reviewed