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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Association of TGF-beta1 and XPD polymorphisms with severe acute radiation-induced esophageal toxicity in locally advanced lung cancer patients treated with radiotherapy.
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Association of TGF-beta1 and XPD polymorphisms with severe acute radiation-induced esophageal toxicity in locally advanced lung cancer patients treated with radiotherapy.

机译:TGF-β1和XPD基因多态性与放疗治疗的局部晚期肺癌患者的严重急性放射诱发的食管毒性相关。

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PURPOSE: Radiation-induced esophageal toxicity (RIET) is a dose-limiting toxicity in lung cancer patients receiving radiotherapy. Accumulating evidence indicates that DNA repair and the cytokine pathways play essential roles in radiation-induced diseases. Genetic polymorphisms of genes in these pathways may affect gene function and/or gene expression and lead to different treatment-related esophageal toxicity. MATERIALS AND METHODS: This study investigated the association of 21 polymorphisms in 14 genes, with the occurrence of >/= grade 2 acute RIET. Genotypes were analyzed among 213 stage III lung cancer patients receiving radiotherapy. RESULTS: We used Cox proportional hazard model to examine the effects of genotypes on >/= grade 2 acute RIET risk and Kaplan-Meier estimator to compare effects of different genotypes on such risk. Multivariate analysis showed that CT or TT genotype of TGF-beta1-509C/T polymorphism was associated with a significantly higher RIET risk (adjusted hazard ratio [HR]=2.47; 95% confidence interval (CI)=1.17-5.24; P=0.018, or HR=3.86; 95% CI=1.50-9.92; P=0.005), respectively, compared with the CC genotype. Moreover, Lys/Gln+Gln/Gln genotypes of XPD Lys751Gln polymorphism were also associated with a significantly decreased RIET risk (adjusted HR=0.55; 95% CI=0.32-0.96; P=0.030). CONCLUSIONS: This report, for the first time, examined the influence of inherited variation in the DNA repair and the cytokine pathways on RIET.
机译:目的:辐射诱发的食管毒性(RIET)是接受放射治疗的肺癌患者的剂量限制性毒性。越来越多的证据表明,DNA修复和细胞因子途径在辐射诱发的疾病中起着至关重要的作用。这些途径中基因的遗传多态性可能影响基因功能和/或基因表达,并导致与治疗相关的不同食道毒性。材料与方法:本研究调查了14个基因中21种多态性与> / = 2级急性RIET的发生的关系。在213名接受放射治疗的III期肺癌患者中分析了基因型。结果:我们使用Cox比例风险模型检查基因型对> / = 2级急性RIET风险的影响,并使用Kaplan-Meier估计量比较不同基因型对此类风险的影响。多变量分析显示,TGF-beta1-509C / T基因多态性的CT或TT基因型与RIET风险显着较高相关(校正风险比[HR] = 2.47; 95%置信区间(CI)= 1.17-5.24; P = 0.018) ,或HR = 3.86; 95%CI = 1.50-9.92; P = 0.005)。此外,XPD Lys751Gln多态性的Lys / Gln + Gln / Gln基因型也与RIET风险显着降低有关(调整后的HR = 0.55; 95%CI = 0.32-0.96; P = 0.030)。结论:本报告首次检查了DNA修复和细胞因子途径中遗传变异对RIET的影响。

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