title: Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery.
abstract: OBJECTIVE
  To evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy.
  
  
  METHODS
  Skin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood.
  
  
  RESULTS
  In the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015-4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220-5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001-1.293, P=0.048), boost dose-fractionation (3 Gy vs. no boost, OR: 4.902, 95% CI: 1.458-16.483, P=0.010) and ≥ grade 2 acute radiation skin toxicity in breast cancer patients.
  
  
  CONCLUSIONS
  As our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance.
authors.affiliation: University of Piemonte Orientale Amedeo Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica, Novara, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Terrazzino
authors.forename: Pierdaniele
authors.initials: P
authors.lastname: La Mattina
authors.forename: Laura
authors.initials: L
authors.lastname: Masini
authors.forename: Tina
authors.initials: T
authors.lastname: Caltavuturo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Gambaro
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
authors.forename: Marco
authors.initials: M
authors.lastname: Krengli
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D004268:DNA-Binding Proteins / Q000235:genetics*; D019583:Dose Fractionation, Radiation; D005260:Female; D005838:Genotype; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012867:Skin / Q000528:radiation effects*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III