Elisabetta Falvo et al., 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. BMC Cancer
Elisabetta Falvo1, Lidia Strigari2, Gennaro Citro1, Carolina Giordano3, Stefano Arcangeli3, Antonella Soriani2, Daniela D’Alessio2, Paola Muti4, Giovanni Blandino5, Isabella Sperduti4 and Paola Pinnarò3
1Laboratory of Pharmacokinetic/Pharmacogenomic, Regina Elena National Cancer Institute
2Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute
3Department of Radiation Oncology, Regina Elena National Cancer Institute
4Scientiphic Direction, Regina Elena National Cancer Institute
5Transational Oncogenomic Unit, Regina Elena National Cancer Institute
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.
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.
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.
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