TY - JOUR
T1 - Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery
AU - Terrazzino, Salvatore
AU - Mattina, Pierdaniele La
AU - Masini, Laura
AU - Caltavuturo, Tina
AU - Gambaro, Giuseppina
AU - Canonico, Pier Luigi
AU - Genazzani, Armando A.
AU - Krengli, Marco
N1 - Funding Information:
This work was funded by grants from Fondazione della Comunità del Novarese, by Regione Piemonte, Ricerca Sanitaria Finalizzata to AAG (2006) and to PLC (2003, 2007 and 2008).
PY - 2012/5
Y1 - 2012/5
N2 - 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 (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.
AB - 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 (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.
KW - Acute skin reaction
KW - Breast cancer
KW - Radiotherapy
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=84860433204&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2011.12.002
DO - 10.1016/j.radonc.2011.12.002
M3 - Article
SN - 0167-8140
VL - 103
SP - 199
EP - 205
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 2
ER -
