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Genetic Pathways for the Prediction of the Effects of Ionising Radiation: Low Dose Radiosensitivity and Risk to Normal Tissue after Radiotherapy

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Genetic component of sensitivity to radiotherapy

Radiation therapy (RT) in conjunction with chemotherapy and surgery is used to treat many forms of cancer. European researchers have investigated the phenomenon of low-dose radiation sensitivity which can lead to permanent damage of normal tissue many years after treatment.

Health

Although usually effective against cancer, around 5 % of patients show extreme sensitivity of normal tissue to radiation. Adverse effects can occur early on or many years later. As delayed effects can be permanent, a treatment strategy where there are dose constraints for sensitive patients would be beneficial. Little is known about biological factors involved in normal tissue complications and the Genepi-Lowrt project aimed to explore the links between modulation of gene expression after treatment and the development of severe normal tissue toxicity to radiation. The researchers also investigated how genetic factors can be associated with individual sensitivity. Project researchers availed of 108 tissue samples from breast cancer patients from the 'Genetic pathways for the prediction of the effects of ionising radiation’ (Genepi) bio-bank.The scientists looked at whether different genome responses could be linked with inter-individual genetic differences. Significant differences in gene expression were observed at high and low radiation doses. Several candidate biomarkers were identified from bioinformatic analysis of gene profiles from lymphocytes and skin fibroblasts. However, no robust classifier for late adverse effects was identified. Genepi-Lowrt research has provided a firm knowledge base for future research into extreme sensitivity to radiotherapy. Data collected will also be of importance in environmental, diagnostic and occupational exposure to radiation studies.

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