title: Dose and polymorphic genes xrcc1, xrcc3, gst play a role in the risk of articledeveloping erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery.
abstract: BACKGROUND
  To evaluate the association between polymorphisms involved in DNA repair and oxidative stress genes and mean dose to whole breast on acute skin reactions (erythema) in breast cancer (BC) patients following single shot partial breast irradiation (SSPBI) after breast conservative surgery.
  
  
  METHODS
  Acute toxicity was assessed using vers.3 criteria. single nucleotides polymorphisms(SNPs) in genes: XRCC1(Arg399Gln/Arg194Trp), XRCC3 (A4541G-5'UTR/Thr241Met), GSTP1(Ile105Val), GSTA1 and RAD51(untranslated region). SNPs were determined in 57 BC patients by the Pyrosequencing analysis. Univariate(ORs and 95% CI) and logistic multivariate analyses (MVA) were performed to correlate polymorphic genes with the risk of developing acute skin reactions to radiotherapy.
  
  
  RESULTS
  After SSPBI on the tumour bed following conservative surgery, grade 1 or 2 acute erythema was observed in 19 pts(33%). Univariate analysis indicated a higher significant risk of developing erythema in patients with polymorphic variant wt XRCC1Arg194Trp, mut/het XRCC3Thr241Met, wt/het XRCC3A4541G-5'UTR. Similarly a higher erythema rate was also found in the presence of mut/het of XRCC1Arg194Trp or wt of GSTA1. Whereas, a lower erythema rate was observed in patients with mut/het of XRCC1Arg194Trp or wt of XRCC1Arg399Gln. The mean dose to whole breast(p = 0.002), the presence of either mut/het XRCC1Arg194Trp or wt XRCC3Thr241Met (p = 0.006) and the presence of either mut/het XRCC1Arg194Trp or wt GSTA1(p = 0.031) were confirmed as predictors of radiotherapy-induced erythema by MVA.
  
  
  CONCLUSIONS
  The Whole breast mean dose together with the presence of some polymorphic genes involved in DNA repair or oxidative stress could explain the erythema observed after SSPBI, but further studies are needed to confirm these results in a larger cohort.
authors.affiliation: Laboratory of Pharmacokinetic/Pharmacogenomic, Regina Elena National Cancer Institute, Rome, Italy. falvo@ifo.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Falvo
authors.forename: Lidia
authors.initials: L
authors.lastname: Strigari
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Carolina
authors.initials: C
authors.lastname: Giordano
authors.forename: Stefano
authors.initials: S
authors.lastname: Arcangeli
authors.forename: Antonella
authors.initials: A
authors.lastname: Soriani
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Alessio
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Paola
authors.initials: P
authors.lastname: Pinnarò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004890:Erythema / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D051135:Rad51 Recombinase / Q000235:genetics; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D051135:Rad51 Recombinase