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genrad-t_projrep_ en

Project ID: FIGH-CT-2002-00208
Funded under: FP5-EAECTP C


The strategies available for estimating the risk of detrimental health effects after exposure to ionising radiation are changing rapidly. Research conducted by Euratom-funded laboratories and others has firmly established that genetic factors lay a role in influencing biological responses to ionising radiation. The conventional approach to risk estimations has been established by large-scale epidemiological studies of radiationinduced cancers in exposed populations. However, more recent evidence, showing the contribution of individual genetic background to this baseline risk, is now being considered as a significantly modifying influence of individual risk. Thus, the unique genetic composition of each individual will play a role in determining the extent of his or her biological response to ionising radiation. This phenotypic variation may be expressed both in a radiation-specific manner, i.e. in terms of the rate and extent of the repair of initial DNA and cellular damage, and in a non-radiation specific manner, such as the proliferative response to local cell losses, or one of many other general mechanisms promoting/modulating the progression of malignant disease such as neo-angiogenesis, apoptotic activity etc.
Thyroid cancer is a classical model of radiation-induced disease. Causality has been established in both epidemiological and animal experimental studies, demonstrating the link between both local external irradiation and internal contamination with radioiodine. Mechanistically, the principal genetic alterations underlying sporadic thyroid cancer are known, and appear to a large extent to be reflected also in the changes seen in radiationinduced tumours. However, despite the wealth of biological material and dosimetry data, progress towards an elucidation of the genetic basis of individual variability to thyroid cancer has been slow. It is unclear at the moment if population-based studies will ever be able to offer insight into the process.

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