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Title: XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

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 tomore » −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.« less
Authors:
;  [1] ;  [2] ;  [1] ; ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [8] ;  [9] ;  [10] ;  [11] ; ;  [12] ;  [6] ;  [13] ;
  1. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany)
  2. Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg (Germany)
  3. Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, United Kingdom (UK) (United Kingdom)
  4. Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom)
  5. Department of Genetics, University of Leicester, Leicester (United Kingdom)
  6. Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, Chiba (Japan)
  7. Department of Radiation Oncology and Medical Physics, I.C.M. – Institut regional du Cancer Montpellier, Montpellier (France)
  8. Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada)
  9. Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge (United Kingdom)
  10. Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, University of Cambridge, Cambridge (United Kingdom)
  11. The Institute of Cancer Research, Clinical Trials and Statistics Unit, Sutton (United Kingdom)
  12. Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester (United Kingdom)
  13. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NH (United States)
Publication Date:
OSTI Identifier:
22462405
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 92; Journal Issue: 5; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMAL TISSUES; EXCISION REPAIR; FEDERAL REPUBLIC OF GERMANY; FIBROSIS; GENES; HAZARDS; MAMMARY GLANDS; MULTIVARIATE ANALYSIS; NEOPLASMS; NUCLEOTIDES; PATIENTS; RADIOTHERAPY; SKIN; STRESSES; TOXICITY