Predictive Value of Xrcc1 Gene Polymorphisms for Side Effects in Patients undergoing Whole Breast Radiotherapy: a Metaanalysis

Abstract

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repairradiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role inthe repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association betweenXRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effectsin patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine thepredictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity thanthose with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR,1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combinationwith chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele wasassociated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allelevs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protectiveagainst radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs.Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may beindependent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selectionof genotyping method is an important factor in determining risk factors. No evidence for any predictive valueof XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be requiredto further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patientsundergoing whole breast radiotherapy.