title: Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer.
abstract: OBJECTIVE
  Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G.
  
  
  METHODS
  Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED).
  
  
  RESULTS
  Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03).
  
  
  CONCLUSIONS
  Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients.
authors.affiliation: Clinical Biochemistry Unit, Department of Clinical Physiopathology, University of Florence, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pratesi
authors.forename: Monica
authors.initials: M
authors.lastname: Mangoni
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paiar
authors.forename: Lisa
authors.initials: L
authors.lastname: Simi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Livi
authors.forename: Sara
authors.initials: S
authors.lastname: Cassani
authors.forename: Michela
authors.initials: M
authors.lastname: Buglione
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Camillo
authors.initials: C
authors.lastname: Almici
authors.forename: Caterina
authors.initials: C
authors.lastname: Polli
authors.forename: Calogero
authors.initials: C
authors.lastname: Saieva
authors.forename: Stefano Maria
authors.initials: SM
authors.lastname: Magrini
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Biti
authors.forename: Mario
authors.initials: M
authors.lastname: Pazzagli
authors.forename: Claudio
authors.initials: C
authors.lastname: Orlando
mesh_terms: D000328:Adult; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D016009:Chi-Square Distribution; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D051135:Rad51 Recombinase / Q000235:genetics*; D011832:Radiation Injuries / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011879:Radiotherapy Dosage; D017382:Reactive Oxygen Species; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C495153:RAD51 protein, human; D051135:Rad51 Recombinase