Abstract
PurposeFollowing the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC.MethodsWe investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized.ResultsThere were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples.ConclusionSignificant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-015-3303-3) contains supplementary material, which is available to authorized users.
Highlights
Following the nuclear accidents in Chernobyl and 25 years later in Fukushima, the nuclear community has been faced with two important issues: first how to manage radiation contamination, and second how to search for and diagnose biological consequences of low-dose internal radiation contamination
Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples
Significant, but subtle, differences in gene expression in the post-Chernobyl papillary thyroid carcinomas (PTCs) are associated with previous low-dose radiation exposure
Summary
Following the nuclear accidents in Chernobyl and 25 years later in Fukushima, the nuclear community has been faced with two important issues: first how to manage radiation contamination, and second how to search for and diagnose biological consequences of low-dose internal radiation contamination. Some studies have shown only distinct types of RET/PTC rearrangement in patients with radiation-associated and sporadic cancer [10, 11] or a difference between radiation-induced and sporadic PTC using immunohistochemical, genomic and proteomic approaches [14,15,16]. These results could have been biased by many confounding factors (for review see Maenhaut et al [17]) since, except in one study [15], they were not controlled for the potential impact of genetic and environmental factors, patient age, histological variant or stage of disease
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have