Predictive value of single nucleotide polymorphisms in XRCC1 for radiation-induced normal tissue toxicity

PURPOSE: X-Ray Repair Cross Complementing 1 (XRCC1) functioning in the base excision repair pathway plays an important role in the repair of DNA single-strand breaks caused by ionizing radiation. The relationship between XRCC1 polymorphisms and the risk of radiation-induced side effects on normal tissues remains controversial. Therefore, we performed a comprehensive meta-analysis to elucidate these associations. MATERIALS AND METHODS: A systematic literature search was carried out in PubMed, Medline (Ovid), Embase, Web of Science, Cochrane database, and the references of relevant studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. RESULTS: A total of 40 studies including 6,682 patients were eventually identified in this meta-analysis. Pooled results suggested that rs25487 Arg399Gln polymorphism significantly increased the risk of acute radiation-induced side effects (OR=1.29, 95% CI: 1.10–1.52, P=0.002), especially acute mucositis (OR=1.91, 95% CI: 1.17–3.11, P=0.01) and acute gastrointestinal and genitourinary toxicity (OR=1.49, 95% CI: 1.04–2.11, P=0.03). Furthermore, patients who received head and neck irradiation with rs25487 Arg399Gln polymorphism were more likely to experience radiotherapy (RT)-induced side effects (OR=1.46, 95% CI: 1.12–1.90, P=0.005). However, no statistically significant correlations were identified between rs25487 polymorphism and any late side effects and other irradiation areas. Likewise, no significant associations were detected between rs25489, rs1799782, or rs3213245 polymorphism and RT-induced toxicity. CONCLUSION: Our meta-analysis demonstrated that XRCC1 rs25487 Arg399Gln polymorphism had a significant predictive value and might predict a risk of severely acute RT-induced adverse effects, especially in acute mucositis and acute gastrointestinal and genitourinary toxicity, or in patients with head and neck irradiation. However, large-scale and well-designed studies are required to further evaluate the predictive value of XRCC1 variations on radiation-induced side effects in order to identify radiosensitive patients and predict radiotoxicity.