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Communication Dans Un Congrès Année : 2019

Integrating epidemiology and biology for radiation risk assessment

Résumé

Epidemiology has been the main source of scientific information on the health effects of ionizing radiation in humans, which has been used to define radiation protection standards. Although most informative epidemiological data cover the dose range above 100 mGy of low LET radiation, epidemiology is also proving increasingly informative at lower dose levels. It is clear however that below certain dose levels (yet to be determined, depending on the health outcomes considered and possibly population characteristics), the challenges faced by classical epidemiology (especially, statistical power) will prevent it from providing directly informative risk quantification. Integration of epidemiological and biological (including experimental) knowledge is expected to improve radiation risk assessment, notably to further inform risk extrapolation to very low doses. A first way to do this is molecular epidemiology. The feasibility and usefulness of molecular epidemiology studies in radiation research have been extensively discussed as part of DoReMi, OPERRA, MELODI and CONCERT. At a more general level, the Adverse Outcome Pathway (AOP) concept can provide a global framework to structure and integrate knowledge on the effects of low dose radiation. AOPs decompose phenomena demonstrated (and hypothesized) to be of importance in the process of disease development, from the molecular initiating events (i.e. directly resulting from radiation exposure), to the Adverse Outcome (e.g.: disease). Intermediate (“key”) events occurring at several steps (e.g.: at the cellular, tissue, organ levels) of this process are then properly ordered. AOPs can help to identify data gaps to be filled in to improve the understanding and the quantification of relationships between key events. AOPs, have little been developed in the radiation field, but hold great promise to become helpful in improving risk assessment at low doses. For that purpose, AOPs as a flexible framework can and should integrate knowledge from experimental data, as well as from molecular and classical epidemiology. The concept of AOP provides a unique playground where, using the “meet-in-the-middle” approach, knowledge coming from studies on radiosusceptibility, biomarkers of exposure and mechanistic cellular and tissue effects defining key events following low dose exposure can all be related to knowledge gained from epidemiological studies on relationships between these biomarkers and subsequent disease risks. Therefore, epidemiological studies and statistical modelling including Biologically Based Dose Response models will be crucial for that purpose. Challenges in developing radiation AOPs include the adequate integration of quantitative relationships and their temporality, integration of quantitative data from various models (human, animal, cell), the expected lack of specificity of many key events and outcomes and the sparsity of biological samples for molecular epidemiology. Integrating epidemiology and biology for radiation risk assessment at low doses will require multidisciplinary efforts, including contribution from the more AOP-experienced non-radiation (e.g. chemical toxicology) community. Such collaborations will also create opportunities for a better characterization of the effects of joint exposures to radiation and possibility for better integrated radiation protection of humans and the environment.
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hal-03150527 , version 1 (23-02-2021)

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  • HAL Id : hal-03150527 , version 1

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Olivier Laurent, Dmitry Klokov, Olivier Armant, Christelle Adam-Guillermin, Laurence Roy, et al.. Integrating epidemiology and biology for radiation risk assessment. European Radiation Protection Week, ERPW 2019, Oct 2019, STOCKHOLM, Sweden. ⟨hal-03150527⟩
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