title: Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer.
abstract: BACKGROUND
  Osteoradionecrosis (ORN) of the mandible is a severe complication of head and neck radiotherapy (RT) treatment, where the impact of individual radiosensitivity has been a suggested explanation.
  
  
  METHODS
  A cohort of patients with stage II/III ORN was compared to matched controls. Blood was collected and irradiated in vitro to study the capacity to handle radiation-induced oxidative stress. Patients were also genotyped for 8 single-nucleotide polymorphisms (SNPs) in genes involved in the oxidative stress response.
  
  
  RESULTS
  A difference in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels was found between the patient cohorts (p = 0.01). The SNP rs1695 in glutathione s-transferase p1 (GSTP1) was also found to be more frequent in the patients with ORN (p = .02). Multivariate analysis of the clinical and biological factors revealed concomitant brachytherapy plus the 2 biomarkers to be significant factors which influense risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer.
  
  
  CONCLUSIONS
  The current study indicates that oxidative stress response contributes to individual radiosensitivity and healthy tissue damage caused by RT and may be predicted by biomarker analysis.
authors.affiliation: Department of Clinical Science, Intervention and Technology, Division of Ear, Nose, and Throat Diseases, Karolinska Institute, Stockholm, Sweden.|Department of Oral and Maxillofacial Surgery, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Danielsson
authors.affiliation: Department of Molecular Bioscience, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Brehwens
authors.affiliation: Department of Molecular Medicine and Surgery, Reconstructive Plastic Surgery, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
authors.affiliation: Data Mining Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Marczyk
authors.affiliation: Department of Molecular Bioscience, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Alice
authors.initials: A
authors.lastname: Sollazzo
authors.affiliation: Data Mining Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Polanska
authors.affiliation: Department of Oto-Rhino-Laryngology, Head and Neck Surgery, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.affiliation: Department of Molecular Bioscience, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.|Institute of Biology, Jan Kochanowski University, Kielce, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
authors.affiliation: Department of Molecular Bioscience, Centre for Radiation Protection Research, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D000068617:Genetic Background; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008334:Mandible / Q000528:radiation effects*; D008336:Mandibular Diseases / Q000209:etiology*; D008875:Middle Aged; D010025:Osteoradionecrosis / Q000209:etiology / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors
keywords: glutathione s-transferase p1 (GSTP1) mutation; head and neck; osteoradionecrosis; oxidative stress; radiotherapy; rs 1695; serum 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG)