Abstract
The X-ray repair cross-complementing group 3 (XRCC3) protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539) polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31–3.01, P = 0.001). A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97–1.68, P = 0.08). In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49–3.89, p = 0.0003) and breast irradiation (OR = 1.41, 95%CI: 1.02–1.95, p = 0.04), whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26–0.86, P = 0.01). Well-designed large-scale clinical studies are required to further validate our results.
Highlights
Radiotherapy is an important and commonly used modality in cancer treatment, but normal tissues both in the vicinity of the target area and the pathway of the radiation beam are inevitably irradiated, which may result in a spectrum of normal tissue adverse effects [1]
For rs861539, six studies evaluated the early adverse effects induced by radiotherapy, while nine studies focused on late adverse effects
Subgroup analysis was conducted by specific adverse effect, and the results indicated that rs861539 significantly correlated with acute skin toxicity (OR = 1.86, 95%confidence intervals (CIs): 1.13–3.05, P = 0.01) and mucositis (OR = 2.89, 95% confidence interval (95%CI): 1.24–6.76, P = 0.01) (Fig 3)
Summary
Radiotherapy is an important and commonly used modality in cancer treatment, but normal tissues both in the vicinity of the target area and the pathway of the radiation beam are inevitably irradiated, which may result in a spectrum of normal tissue adverse effects [1]. The prescribed dose of radiotherapy in most malignant diseases is restricted by the tolerance of normal tissue to radiation [2]. Patients exhibit large variability in normal tissue toxicity even to the same treatment schedule [3]. If the individual risk of adverse effects can be predicted prior to radiotherapy, it would be of great benefit to the personalization and optimization of treatment strategies [5,6]. Single nucleotide polymorphisms (SNPs) account for most known genetic variation [6,8]. By altering the amino acid composition of the encoded proteins, SNPs in DNA repair genes may alter protein function and an individual’s capacity for the repair of damaged DNA [9,10,11]
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