Is Clinical Radiosensitivity a Complex Genetically Controlled Event?

New insights into molecular mechanisms responsible for cellular radiation response are coming from recent basic radiobiological studies. Preliminary data supporting the concept of clinical radiosensitivity as a complex genetically controlled event are available, and it seems reasonable to hypothesize that genes encoding for proteins implicated in known radiation-induced pathways, such as DNA repair, could influence normal tissue and tumor response to radiotherapy. Such genes could be considered as candidates for experimental studies and as targets for innovative therapies. Variants that could influence individual radiosensitivity have been recently identified, and specific Single Nucleotide Polymorphisms have been associated to the development of different radiation effects on normal tissues. Allelic architecture of complex traits able to modify phenotypes is difficult to be established, and different grades of interaction between common or rare genetic determinants may be present and should be considered. Many different experimental strategies could be investigated in the future, such as analysis of multiple genes in large irradiated patient cohorts strictly observed for radiation effects or identification of new candidate genes, with the aim of identifying factors that could be employed in predictive testing and individualization of radiation therapy on a genetic basis.