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» Shape of the dose-response curve for cancer


WP5 Shape of the dose-response curve for cancer


WP5 addresses the scientific question, what is the general shape of the dose-response for radiation-induced cancer and to what extent does it depend on tumour (tissue) type?

The objectives of WP5 are:

  • to improve knowledge of low dose/dose rate radiation cancer risk in humans
  • to improve low dose/dose-rate risk projection models based on knowledge of the processes that drive carcinogenesis


Overall approach

WP5 is currently organised into five tasks:
  • Task 5.1 considers phase-shifts in responses and processes at high/low doses and dose rates. The work centres on studies of stress responses in primary human cells, identifying and validating low dose radiation gene expression profiles and developing in vivo reporter genes of radiation response.
  • Task 5.2 aims to assess the contribution of non-targeted and systemic processes to radiation carcinogenesis. Research priorities for this task were discussed at a workshop held in June 2010. Following the first DoReMi external call a study of the dose-response for theinduction of inflammatory reactions in humans started in July 2011.
  • Task 5.3 focuses on the dynamics of preneoplastic change and clonal development and exploits a well-characterised mouse model of radiation leukaemogenesis.  Experimental work aims to identify key events in carcinogenesis and explore dose-response and time course relationships.
  • Task 5.4 aims to link experimental and epidemiological data through mathematical models, significant interaction and synergy with the recently started EpiRadBio project is expected. 
  • Task 5.5 concerns risks from internal contamination with radionuclides. A major workshop was held in March 2011 to identify research priorities and plan linked epidemiological and experimental study of internal emitter risk. This discussion was successful in identifying priority issues that may inform future calls for proposals.
  • Task 5.6 will start in early 2012. It aims to extend and use the well-established physical-biological Monte Carlo modelling tool PARTRAC to investigate different aspects of initial damage formation and its progression in order to improve predictions of the relative biological effectiveness (RBE) of different radiation qualities, and to integrate modelling with experiments to investigate non-DNA targeted effects at the cellular level.

In addition WP5 expects to run workshops that will help reach consensus on priorities in research areas that may help the WP objectives to be met. To this end a workshop on Stem cells and DNA damage was held in December 2011.