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Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective
Gillian C Barnett1, Charlotte E Coles, Rebecca M Elliott
1University of Cambridge, Department of Oncology, Cambridge, UK. gillbarnett@doctors.org.uk
The Lancet. Oncology
|December 16, 2011
Summary
This study did not replicate previous findings on genetic markers for radiation toxicity. These results suggest that single nucleotide polymorphisms (SNPs) do not individually cause clinically significant effects in patients undergoing radiotherapy.
Area of Science:
- Oncology
- Genetics
- Radiotherapy
Background:
- Previous studies suggested associations between genetic variations (single nucleotide polymorphisms or SNPs) and radiation toxicity.
- However, few of these associations have been validated in independent patient cohorts.
Purpose of the Study:
- To prospectively validate previously reported associations between single nucleotide polymorphisms (SNPs) and the risk of developing late radiation toxicity.
- To assess the clinical relevance of specific SNPs in patients undergoing radiotherapy for breast and prostate cancer.
Main Methods:
- Genotyping of 92 single nucleotide polymorphisms (SNPs) in 46 genes was performed in 1613 patients treated with radiotherapy for breast or prostate cancer.
- Late toxicity was assessed two years post-radiotherapy using clinical evaluation, patient questionnaires, and photographic techniques for breast cancer patients.
- Statistical analyses, including univariate and multivariable models, were used to test associations between genotype and radiation toxicity, with adjustments for multiple testing.
Main Results:
- None of the previously reported associations between SNPs and radiation toxicity were confirmed in this independent cohort after adjusting for multiple comparisons.
- The distribution of p-values for the tested SNPs against the overall toxicity score did not deviate from what would be expected by chance.
Conclusions:
- The study failed to replicate previously reported associations between specific SNPs and late radiation toxicity.
- These findings suggest that individual SNPs likely do not exert a clinically relevant effect on radiation toxicity.
- Further research with larger sample sizes and standardized methodologies within the Radiogenomics Consortium is crucial to address remaining challenges.
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