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目的观察X线修复交错互补基因1(XRCC1)基因399位点(Codon399)单核苷酸多态性(single nucleotide polymorphism,SNP)对食管癌患者急性放射性肺损伤(radiation-induced lung injury,RILI)的影响并探讨其可能的机制。方法收集2012-04-2015-04南通大学附属泰州市人民医院接受放疗的食管癌患者,利用测序法检测接受放疗的食管癌患者XRCC1-Codon399的基因型,ELISA法检测患者放疗前、后血浆中炎症因子(IL-6/TGF-β1)的表达水平,评估≥2级的急性RILI发生情况。观察不同基因型对剂量学参数V5/V20、IL-6/TGF-β1表达以及急性RILI的影响。结果 GA突变型患者急性RILI发生比例高于其他两组基因型(P值分别为0.003,0.009);在发生RILI的患者中,GA突变型患者的V5、V20平均值低于其他表型,P=0.035;不同基因型患者间IL-6、TGF-β1的基线水平无差异,GA突变型患者放疗后IL-6和TGF-β1升高明显,显著高于其他两型,P=0.001。多变量分析显示XRCC1的SNP、V5以及V20均与RILI显著相关。结论 XRCC1-Codon399的SNP对RILI具有预测价值,GA型的患者更易发生RILI且程度更重,在设计放疗计划时需更严格控制V5、V20。
Objective To observe the effect of single nucleotide polymorphism (SNP) at position 399 of XRCC1 gene on radiation-induced lung injury (RILI) in patients with esophageal cancer, Influence and discuss its possible mechanism. Methods To collect the genotypes of XRCC1-Codon399 in esophageal cancer patients undergoing radiotherapy by sequencing and to detect the genotype of XRCC1-Codon399 in patients with esophageal cancer treated with radiotherapy at Taizhou People’s Hospital affiliated to Nantong University 2012-04-2015-04 The level of inflammatory cytokines (IL-6 / TGF-β1) expression was assessed for grade 2 acute RILI. The effects of different genotypes on the parameters of V5 / V20, IL-6 / TGF-β1 and acute RILI were observed. Results The prevalence of acute RILI in patients with GA mutation was higher than those in the other two groups (P = 0.003,0.009, respectively). Among the patients with RILI, the average values of V5 and V20 in patients with GA mutation were lower than those in other phenotypes, P = 0.035. There was no difference in the baseline levels of IL-6 and TGF-β1 among patients with different genotypes. The levels of IL-6 and TGF-β1 in patients with GA mutation were significantly higher than those in other two types of patients after radiotherapy (P = 0.001). Multivariate analysis showed that SNP, V5, and V20 of XRCC1 were significantly associated with RILI. Conclusion The SNP of XRCC1-Codon399 has a predictive value for RILI. Patients with GA type are more likely to develop RILI and are more severe. V5 and V20 should be controlled more strictly when designing radiotherapy plans.