Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery

Terrazzino, Salvatore; Mattina, Pierdaniele La; Masini, Laura; Caltavuturo, Tina; Gambaro, Giuseppina; Canonico, Pier Luigi; Genazzani, Armando A.; Krengli, Marco

doi:10.1016/j.radonc.2011.12.002

« Previous Next »Radiotherapy & Oncology
Volume 103, Issue 2 , Pages 199-205, May 2012

Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery

Salvatore Terrazzino
- University of Piemonte Orientale “Amedeo Avogadro,” DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy
Pierdaniele La Mattina
- University of Piemonte Orientale “Amedeo Avogadro” and Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy
Laura Masini
- University of Piemonte Orientale “Amedeo Avogadro” and Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy
Tina Caltavuturo
- University of Piemonte Orientale “Amedeo Avogadro” and Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy
Giuseppina Gambaro
- University of Piemonte Orientale “Amedeo Avogadro” and Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy
Pier Luigi Canonico
- University of Piemonte Orientale “Amedeo Avogadro,” DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy
Armando A. Genazzani
- University of Piemonte Orientale “Amedeo Avogadro,” DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy
Marco Krengli
- University of Piemonte Orientale “Amedeo Avogadro” and Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy
- Corresponding author. Address: Department of Radiotherapy, University Hospital Maggiore della Carità, Novara, Italy.

Received 27 July 2011; received in revised form 5 October 2011; accepted 10 December 2011. published online 16 January 2012.

Abstract

Purpose

To evaluate the impact of functional polymorphisms in genes related to DNA repair mechanisms (XRCC1, TP53, MSH2, MSH3, XPD), oxidative stress response (GSTP1, GSTA1, eNOS, SOD2) and fibroblast proliferation (TGFβ1) on the risk of acute skin toxicity in breast cancer patients receiving radiotherapy.

Material and methods

Skin toxicity was scored according to the Radiation Therapy Oncology Group criteria in 286 breast cancer patients who received radiotherapy after breast conserving surgery. Genotyping was conducted by PCR-RFLP analysis and real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood.

Results

In the multivariate analysis, nominally significant associations, before multiple testing corrections, were found between XRCC1 T-77C (T carriers vs. CC, OR: 2.240, 95% CI: 1.015–4.941, P=0.046), eNOS G894T polymorphisms (TT vs. G carriers, OR: 2.473, 95% CI: 1.220–5.012, P=0.012), breast diameter (OR: 1.138, 95% CI: 1.001–1.293, P=0.048), boost dose-fractionation (3Gy vs. no boost, OR: 4.902, 95% CI: 1.458–16.483, P=0.010) and ⩾grade 2 acute radiation skin toxicity in breast cancer patients.

Conclusions

As our exploratory study suggests that XRCC1 T-77C and eNOS G874T may confer an increased risk of acute skin reactions to radiotherapy in breast cancer patients, further confirmatory studies are warranted to determine the clinical significance.

Keywords: Acute skin reaction, Breast cancer, Radiotherapy, Single nucleotide polymorphisms