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A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
Published on: April 1, 2019
Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes
Christian Nicolaj Andreassen1, Jan Alsner, Marie Overgaard
1Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, Aarhus C DK 8000, Denmark.
Summary
Genetic variations in genes like TGFB1 and XRCC3 influence radiation injury risk. Specific single nucleotide polymorphisms (SNPs) correlate with increased risk of subcutaneous fibrosis and telangiectasia after radiotherapy, suggesting a polygenic model for radiosensitivity.
Area of Science:
- Genetics
- Radiation Oncology
- Molecular Biology
Background:
- Clinical normal tissue radiosensitivity can be influenced by genetic factors.
- Single nucleotide polymorphisms (SNPs) in radiation response genes are potential determinants of patient outcomes.
- Understanding these genetic links is crucial for personalized radiotherapy.
Purpose of the Study:
- To investigate the association between seven selected SNPs in five candidate genes and the risk of subcutaneous fibrosis and telangiectasia.
- To determine if specific genotypes influence normal tissue reactions following radiotherapy.
- To quantify differences in radiosensitivity based on genetic variations.
Main Methods:
- Analysis of SNPs in TGFB1, SOD2, XRCC3, XRCC1, and APEX genes using PCR and single nucleotide primer extension.
- Evaluation of 41 patients who received post-mastectomy radiotherapy.
- Establishment of dose-response curves and quantification of radiosensitivity (ED(50) values, enhancement ratios) for different genotypes.
Main Results:
- Specific genotypes in TGFB1 (codon 10 Pro/Pro, -509 T/T), SOD2 (codon 16 Val/Ala), XRCC3 (codon 241 Thr/Thr), and XRCC1 (codon 399 Arg/Arg) were positively correlated with increased risk of subcutaneous fibrosis.
- The XRCC3 codon 241 Thr/Thr genotype also correlated with an increased risk of telangiectasia.
- Patients with fewer risk alleles exhibited significantly greater radioresistance, indicating a combined genetic effect.
Conclusions:
- Five SNPs were significantly correlated with the risk of radiation-induced normal tissue reactions.
- Clinical normal tissue radiosensitivity is likely a polygenic trait, influenced by the combined effects of multiple gene variations.
- Models incorporating multiple genetic markers hold potential for predicting individual patient responses to radiotherapy.
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