SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation

Elisabetta Falvo, Lidia Strigari, Gennaro Citro, Carolina Giordano, Genoveva Boboc, Fabiana Fabretti, Vicente Bruzzaniti, Luca Bellesi, Paola Muti, Giovanni Blandino, Paola Pinnarò, Elisabetta Falvo, Lidia Strigari, Gennaro Citro, Carolina Giordano, Genoveva Boboc, Fabiana Fabretti, Vicente Bruzzaniti, Luca Bellesi, Paola Muti, Giovanni Blandino, Paola Pinnarò

Abstract

Background: The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI) after BCS (breast conserving surgery).

Methods: A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms) in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ≥ G2 fibrosis or fat necrosis.

Results: A higher significant risk of developing ≥ G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val) (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047).

Conclusions: The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity.

Trial registration: ClinicalTrials.gov: NCT01316328.

Figures

Figure 1
Figure 1
Polymorphism distribution.
Figure 2
Figure 2
Forest plot summarizes a pooled analysis of G2 or more fibrosis/fat necrosis distinguishing patients with/without XRCC1 399Gln. The mutation is toxic or protective when OR is higher or lower than 1, respectively.
Figure 3
Figure 3
Forest plot summarizes a pooled analysis of G2 or more fibrosis/fat necrosis distinguishing patients with/without het/mut GSTP1. The mutation is toxic or protective when OR is higher or lower than 1, respectively.
Figure 4
Figure 4
GSTP1 rule in stress response system.

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