Studying The Association Between Uranium Exposure And Cancer By Integrating Dosimetry, Radiobiology And Epidemiology: The CURE Project

Olivier LAURENT, French Institute for Radiological Protection and Nuclear Safety (IRSN), France
GOMOLKA M. 2 , HAYLOCK R. 3 , BLANCHARDON E. 1 , GIUSSANI A. 2 , ATKINSON W. 4 , BINGHAM D. 5 , BAATOUT S. 6 , TOMASEK L. 7 , CARDIS E. 8 , HALL J. 9 , LAURIER D. 1

1 Institute for Radiological Protection and Nuclear Safety (IRSN), France
2 Federal Office for Radiation Protection (BfS), Germany
3 Public Health England, UK
4 Nuvia limited, UK
5 Atomic Weapons Establishment plc, UK
6 Belgian Nuclear Research Centre (SCK-CEN), Belgium
7 National Radiation Protection Institute, Prague, Czech Republic
8 Centre for Research in Environmental Epidemiology (CREAL), Spain
9 Inserm, France

Introduction
Uranium is a radionuclide emitting alpha particles, and therefore has potential to be carcinogenic. However, direct evidence that would allow for a proper quantification of the carcinogenic effects of uranium in humans is limited. Especially, most available epidemiological studies suffer from major limitations. New studies borrowing strengths from enhanced epidemiological datasets on the one hand, and from modern biology approaches on the other hand, will have higher potential to improve the characterization of the biological effects of uranium exposure and the quantification of subsequent cancer risk.

Methods
CURE (Concerted Uranium Research in Europe) was a 18-month concerted action supported by the European Commission, involving 9 European institutes. It aimed to elaborate a collaborative research project on the biological and health effects of uranium contamination, integrating epidemiology, biology and dosimetry. A work-package was dedicated to each of these disciplines with strong interactions, and a further working group on uncertainty was constituted. A strong focus was put on cancer effects.

Results
Protocols were developed for pooled analyses of existing cohorts of uranium miners (40,000) and uranium processing workers (40,000) in Belgium, the Czech Republic, France, Germany, and the United Kingdom. To allow for the study of dose-response relationships, protocols were developed to calculate organ doses due to uranium exposure using state-of-the art dosimetric methods. Feasibility studies for molecular epidemiology were worked out for sub-cohorts, and standardized protocols were developed for the measurement of several biomarkers relevant to cancer effects. Methods were proposed to estimate the impacts of uncertainties at several steps of the project.

Conclusions                                                                                          
Based on CURE protocols, a multidisciplinary research project will be proposed to improve the characterization of the biological effects associated with uranium exposure, and the quantification of related cancer risk.
Funding source
European Commission, through the 7th Framework Program Network of Excellence DoReMi (http://www.doremi-noe.net/)