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Title: SNP in TXNRD2 Associated With Radiation-Induced Fibrosis: A Study of Genetic Variation in Reactive Oxygen Species Metabolism and Signaling

Purpose: The aim of the study was to identify noninvasive markers of treatment-induced side effects. Reactive oxygen species (ROS) are generated after irradiation, and genetic variation in genes related to ROS metabolism might influence the level of radiation-induced adverse effects (AEs). Methods and Materials: 92 breast cancer (BC) survivors previously treated with hypofractionated radiation therapy were assessed for the AEs subcutaneous atrophy and fibrosis, costal fractures, lung fibrosis, pleural thickening, and telangiectasias (median follow-up time 17.1 years). Single-nucleotide polymorphisms (SNPs) in 203 genes were analyzed for association to AE grade. SNPs associated with subcutaneous fibrosis were validated in an independent BC survivor material (n=283). The influence of the studied genetic variation on messenger ribonucleic acid (mRNA) expression level of 18 genes previously associated with fibrosis was assessed in fibroblast cell lines from BC patients. Results: Subcutaneous fibrosis and atrophy had the highest correlation (r=0.76) of all assessed AEs. The nonsynonymous SNP rs1139793 in TXNRD2 was associated with grade of subcutaneous fibrosis, the reference T-allele being more prevalent in the group experiencing severe levels of fibrosis. This was confirmed in another sample cohort of 283 BC survivors, and rs1139793 was found significantly associated with mRNA expression level of TXNRD2 in blood.more » Genetic variation in 24 ROS-related genes, including EGFR, CENPE, APEX1, and GSTP1, was associated with mRNA expression of 14 genes previously linked to fibrosis (P≤.005). Conclusion: Development of subcutaneous fibrosis can be associated with genetic variation in the mitochondrial enzyme TXNRD2, critically involved in removal of ROS, and maintenance of the intracellular redox balance.« less
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [3] ;  [1] ;  [2] ; ;  [1] ;  [4] ;  [5] ; ;  [6] ;  [1] ;  [2] ;  [7] ;  [2] ;  [1] ;  [2] ;  [8]
  1. Department of Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo (Norway)
  2. (Norway)
  3. National Resource Centre for Late Effects after Cancer Treatment, OUS Radiumhospitalet, Oslo (Norway)
  4. Department of Medical Sciences, Uppsala University, Uppsala (Sweden)
  5. Department of Medical Genetics, OUS Ullevaal, Oslo (Norway)
  6. Department of Experimental Clinical Oncology, Ahus University Hospital (Norway)
  7. K. G. Jebsen Breast cancer centre, Institute for Clinical Medicine, University of Oslo, Oslo (Norway)
  8. (EpiGen), Division of Medicine, Ahus University Hospital (Norway)
Publication Date:
OSTI Identifier:
22224543
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 86; Journal Issue: 4; Other Information: Copyright (c) 2013 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; ATROPHY; AUGER ELECTRON SPECTROSCOPY; BLOOD; ENZYMES; FIBROBLASTS; FIBROSIS; GENES; IRRADIATION; LUNGS; MESSENGER-RNA; METABOLISM; MITOCHONDRIA; NEOPLASMS; NUCLEOTIDES; RADIOTHERAPY; SIDE EFFECTS