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Open Access Research article

Dose and polymorphic genes xrcc1, xrcc3, gst play a role in the risk of developing erythema in breast cancer patients following single shot partial breast irradiation after conservative surgery

Elisabetta Falvo1*, Lidia Strigari2, Gennaro Citro1, Carolina Giordano3, Stefano Arcangeli3, Antonella Soriani2, Daniela D'Alessio2, Paola Muti4, Giovanni Blandino5, Isabella Sperduti6 and Paola Pinnarò3

Author Affiliations

1 Laboratory of Pharmacokinetic/Pharmacogenomic, Regina Elena National Cancer Institute, Rome, Italy

2 Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome, Italy

3 Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy

4 Scientiphic Direction, Regina Elena National Cancer Institute, Roma, Italy

5 Transational Oncogenomic Unit, Regina Elena National Cancer Institute, Roma, Italy

6 Scientific Director Office, Regina Elena National Cancer Institute, Roma, Italy

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BMC Cancer 2011, 11:291  doi:10.1186/1471-2407-11-291

Published: 12 July 2011

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 Identifier: NCT01316328