XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer PatientsCitation formats
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XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients. / Seibold, Petra; Behrens, Sabine; Schmezer, Peter; Helmbold, Irmgard; Barnett, Gillian; Coles, Charlotte; Yarnold, John; Talbot, Christopher J; Imai, Takashi; Azria, David; Koch, C Anne; Dunning, Alison M; Burnet, Neil; Bliss, Judith M; Symonds, R Paul; Rattay, Tim; Suga, Tomo; Kerns, Sarah L; Bourgier, Celine; Vallis, Katherine A; Sautter-Bihl, Marie-Luise; Claßen, Johannes; Debus, Juergen; Schnabel, Thomas; Rosenstein, Barry S; Wenz, Frederik; West, Catharine M; Popanda, Odilia; Chang-Claude, Jenny.
In: International Journal of Radiation: Oncology - Biology - Physics, Vol. 92, No. 5, 01.08.2015, p. 1084-1092.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients
AU - Seibold, Petra
AU - Behrens, Sabine
AU - Schmezer, Peter
AU - Helmbold, Irmgard
AU - Barnett, Gillian
AU - Coles, Charlotte
AU - Yarnold, John
AU - Talbot, Christopher J
AU - Imai, Takashi
AU - Azria, David
AU - Koch, C Anne
AU - Dunning, Alison M
AU - Burnet, Neil
AU - Bliss, Judith M
AU - Symonds, R Paul
AU - Rattay, Tim
AU - Suga, Tomo
AU - Kerns, Sarah L
AU - Bourgier, Celine
AU - Vallis, Katherine A
AU - Sautter-Bihl, Marie-Luise
AU - Claßen, Johannes
AU - Debus, Juergen
AU - Schnabel, Thomas
AU - Rosenstein, Barry S
AU - Wenz, Frederik
AU - West, Catharine M
AU - Popanda, Odilia
AU - Chang-Claude, Jenny
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.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.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).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.
AB - 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.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.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).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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Alleles
KW - Breast
KW - Breast Neoplasms
KW - Cohort Studies
KW - DNA-Binding Proteins
KW - Female
KW - Fibrosis
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Germany
KW - Humans
KW - Middle Aged
KW - Odds Ratio
KW - Oxidative Stress
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Predictive Value of Tests
KW - Radiation Injuries
KW - Radiation Tolerance
KW - X-ray Repair Cross Complementing Protein 1
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ijrobp.2015.04.011
DO - 10.1016/j.ijrobp.2015.04.011
M3 - Article
C2 - 26072091
VL - 92
SP - 1084
EP - 1092
JO - International Journal of Radiation: Oncology - Biology - Physics
JF - International Journal of Radiation: Oncology - Biology - Physics
SN - 0360-3016
IS - 5
ER -