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

Elisabetta Falvo, Lidia Strigari, Gennaro Citro, Carolina Giordano, Stefano Arcangeli, Antonella Soriani, Daniela D'Alessio, Paola Muti, Giovanni Blandino, Isabella Sperduti, Paola Pinnarò, Elisabetta Falvo, Lidia Strigari, Gennaro Citro, Carolina Giordano, Stefano Arcangeli, Antonella Soriani, Daniela D'Alessio, Paola Muti, Giovanni Blandino, Isabella Sperduti, Paola Pinnarò

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.

Materials and 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.

Trial registration: ClinicalTrials.gov NCT01316328.

Figures

Figure 1
Figure 1
Typical raw data obtained using Pyrosequencing instruments for GSTA1 and XRCC1 Arg194Trp polymorphisms. Note: the yellow area indicates the resulting genotypes of GSTA1 and XRCC1 Arg194Trp.
Figure 2
Figure 2
(a) Forest plot summarizes a pooled analysis of acute erythema distinguishing patients with/without (A) wt XRCC1 Arg194Trp; (B) wt XRCC3 Thr241Met; (C) wt XRCC1 Arg399Gln; (D) GSTA1; (E) GSTP1. The mutation is toxic or protective when OR is higher or lower than 1, respectively.

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