Last update on October 2015
The CURE (Concerted Uranium Research in Europe) project was coordinated by IRSN in 2013 and 2014. It aimed to develop an innovative approach that integrates epidemiology, biology, dosimetry, toxicology and statistics to expand knowledge of the health effects of chronic uranium exposure and produce a protocol for a collaborative European research project on the topic.
Context and purpose
There is still a lack of understanding of the health effects from uranium intake, particularly for chronic exposure to low doses. Experimental studies on the effect of uranium have reported biological effects, but their implications to human health are not clear yet. Doses resulting from uranium exposure in the workplace have not been estimated using harmonized approaches in existing epidemiological studies. In addition, most of the cohorts studied are limited in size and therefore lack statistical power. Studies carried out until now are therefore insufficient to conclude whether or not health effect exist following chronic exposure to low doses of uranium.
The CURE project sought to develop a new study based on modern biological approaches, joint analysis of the main cohorts of workers monitored for uranium exposure, and the latest internal dose calculation models. This three-pronged approach aimed to improve the potential for characterizing the biological and health effects of chronic exposure to low doses of uranium.
This 18-month project brought together 9 European partners for a joint action supported by the
DoReMi network of excellence. The CURE study assessed the possibility of pooling data from cohorts of workers exposed to uranium who were monitored across different countries, in order to increase the statistical power available for risk analysis. Furthermore, the CURE study developed a standardized methodology to estimate the internal dose in these cohorts. Finally, one of the study's most innovative objectives was to assess the possibility of integrating radiobiological research into epidemiological studies to gain a better understanding of the biological and health effects of uranium on humans.
The CURE study had two main objectives:
- to prepare a shared protocol for epidemiological analysis of cohorts of nuclear workers and uranium miners in Europe by standardizing dose estimation methods in order to directly estimate the potential health risks associated with chronic uranium exposure;
- to assess the feasibility of a molecular epidemiological approach (quantification of exposure biomarkers and development of modern biobanks) in cohorts of workers and develop a shared protocol for the implementation of a European molecular epidemiology study.
The project reviewed the most relevant European cohorts to analyze the risk of cancerous and non-cancerous diseases associated with uranium (uranium miners exposed to low radon levels in France, Germany and the Czech Republic; uranium cycle workers in France, the UK and Belgium). A multi-disciplinary integrated research protocol was developed using existing expertise in epidemiology, dosimetry, biology, toxicology and statistics in the different partner bodies.
The research protocol that was developed could be implemented in the short term. It is available in the
CURE project's final report, published in March 2015.
- confirms the feasibility of pooling cohorts of nuclear workers and uranium miners from five European countries to carry out joint analyses;
- helped define standardized dose calculation methods for all cohorts;
confirms the feasibility of a molecular epidemiological approach (implementation of standardized operational procedures for the collection and transport of biological material, validation of relevant biomarkers, etc.).
More precisely, the CURE project paved the way for a multi-disciplinary study with three levels of analysis: estimation of the mortality ratio of cohorts of workers compared to the general population, estimation of the correlations between uranium exposure and the risk of (cancerous and non-cancerous) diseases, and estimation of the link between uranium exposure and relevant biomarkers for the study of the biological and health effects of this radionuclide. It also identified relevant subgroups for the three levels of analysis in the existing epidemiological cohorts. The regulatory authorizations required in each country were reviewed and a standardized questionnaire and consent form for the sampling of biological material was developped.
The feasibility of developing a modern biobank from cohorts of active workers was validated. Such biobanks could become key infrastructure for integrated radiobiological and molecular epidemiological research into the effects of chronic exposure to radionuclides, and more generally, for research in the field of radiation protection.
The study protocol developed within the CURE project could be implemented, provided the necessary collaborative agreements are put in place and specific funding is obtained. It is possible to extend protocol implementation to other countries outside of Europe in order to increase the study's statistical power and adapt it to other situations of exposure to internal contamination.
- Gueguen Y, Rouas C.
Données nouvelles sur la néphrotoxicité de l'uranium. Radioprotection (2012) 47.
- Guseva Canu I, et al. Uranium carcinogenicity in humans might depend on the physical and chemical nature of uranium and its isotopic composition: results from pilot epidemiological study of French nuclear workers. Cancer causes & control: CCC (2011) 22:1563-1573.
- Laurent O, et al. DoReMi - Low Dose Research towards Multidisciplinary Integration. D5.17: Report for an integrated (biology- dosimetry-epidemiology) research project on occupational uranium exposure. Task5.8: Concerted Uranium Research in Europe (CURE), final report. Feb 2015.
- Lestaevel P, Houpert P, Bussy C, Dhieux B, Gourmelon P, Paquet F. The brain is a target organ after acute exposure to depleted uranium. Toxicology (2005) 212:219-226.
- Zhivin S, Laurier D, Guseva Canu I. Health effects of occupational exposure to uranium: do physicochemical properties matter?
Int J Radiat Biol. 2014 Nov;90(11):1104-13
- Grison S, Favé G, Maillot M, Manens L, Delissen O, Blanchardon E, Banzet N, Defoort C, Bott R, Dublineau I, Aigueperse J, Gourmelon P, Martin JC, Souidi M. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples. Metabolomics. 2013;9(6):1168-1180.