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Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype

Abstract

A key challenge in radiotherapy is to maximize radiation doses to cancer cells while minimizing damage to surrounding healthy tissue. As severe toxicity in a minority of patients limits the doses that can be safely given to the majority, there is interest in developing a test to measure an individual's radiosensitivity before treatment. Variation in sensitivity to radiation is an inherited genetic trait and recent progress in genotyping raises the possibility of genome-wide studies to characterize genetic profiles that predict patient response to radiotherapy.

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Figure 1: Dose–response curves for radiotherapy.
Figure 2: The toxicity of radiotherapy.
Figure 3: Proposed design for a radiation toxicity genome-wide association study (GWAS).

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Acknowledgements

The work of the authors is supported by Cancer Research UK, The Royal College of Radiologists, Breast Cancer Campaign, the National Institute for Health Research Cambridge Biomedical Research Centre, and Experimental Cancer Research Centre funding. G.C.B. is funded by a fellowship from Cancer Research UK and The Royal College of Radiologists. P.D.P.P. is a Cancer Research UK Senior Clinical Research Fellow.

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Correspondence to Gillian C. Barnett.

Supplementary information

Supplementary information S1 (table)

Published candidate gene studies linking genotype with radiotherapy toxicity (PDF 159 kb)

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DATABASES

OMIM

ataxia telangiectasia

Bloom's syndrome

Fanconi's anaemia

Nijmegen breakage syndrome

FURTHER INFORMATION

ASTRO

Cancer Research UK Department of Oncology at Strangeways

CTCAE v3.0

ESTRO

International Agency for Research on Cancer

International HapMap Project

The NIEHS SNPs Program

SeattleSNPs

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Barnett, G., West, C., Dunning, A. et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 9, 134–142 (2009). https://doi.org/10.1038/nrc2587

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