The Potential Utilization of DNA Repair Protein XRCC1 as a Predictive Biomarker for Radiotherapy Response in Iraqi Women with Breast Cancer

Abstract

This study sought to elucidate whether the XRCC1 protein could serve as a predictive biomarker for treatment response in breast cancer (BC) women undergoing radiotherapy (RT). Between July 2024 and January 2025, 180 blood samples from 60 newly diagnosed BC patients, aged 34–56 years, before and after RT at the Al-Amal National Hospital for Cancer Management and the Baghdad Center for Nuclear Medicine and Radiotherapy, as well as 60 age- and sex-matched controls (30 RT workers and 30 healthy women), were tested. A made-on-request enzyme immunoassay measured XRCC1 levels. Serum XRCC1 levels in BC patients significantly increased after RT, followed by RT workers, compared to pre-RT patients and healthy controls (438.42±105.18 vs 348.58±104.56 vs 53.36±13.97 vs 93.71±27.56 pg/ml, P<0.001). In BC patients receiving RT, XRCC1 levels were higher in the 15-fraction and 30-fraction groups than the 20- and 25-fraction groups (449.95±105.48 vs 538.59±4.63 vs 336.18±3.01 vs 368.12±80.16 pg/ml, P<0.05). XRCC1 levels were elevated significantly with RT doses of ≥ 50 Gy and 45 Gy (570.33±45.07 and 472.47±66.92 pg/ml). RT at 6 and 10 MV did not significantly affect BC patients (449.39±101.35 vs. 428.83±109.11 pg/ml, P>0.05). The XRCC1 ROC curve showed a high AUC (0.801, 95% CI= 0.70-0.88) with 74.5% sensitivity and 89.7% specificity. Additionally, XRCC1 predicted RT response with 81% accuracy (95% CI= 71.48-88.52). In BC patients and RT workers, high XRCC1 levels were linked to RT parameters, suggesting that XRCC1 may predict RT responsiveness and DNA repair efficacy. XRCC1 may also predict radiation-induced DNA damage in RT workers and encourage greater radiation protection.