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XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2015 Aug 01; Vol. 92 (5), pp. 1084-1092. Date of Electronic Publication: 2015 Apr 11. - Publication Year :
- 2015
-
Abstract
- Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress-related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy.<br />Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence.<br />Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (-0.08, 95% confidence interval -0.15 to -0.02, P=.016).<br />Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Alleles
Breast pathology
Cohort Studies
Female
Fibrosis genetics
Genome-Wide Association Study
Germany
Humans
Middle Aged
Odds Ratio
Oxidative Stress genetics
Phenotype
Predictive Value of Tests
Radiation Injuries pathology
Radiation Tolerance genetics
X-ray Repair Cross Complementing Protein 1
Breast radiation effects
Breast Neoplasms genetics
Breast Neoplasms radiotherapy
DNA-Binding Proteins genetics
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Radiation Injuries genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-355X
- Volume :
- 92
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 26072091
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2015.04.011