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

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 (TGF beta 1) 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 (3 Gy 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 103 (2012) 199-205