Aguado-Barrera Miguel E, Martínez-Calvo Laura, Fernández-Tajes Juan, Calvo-Crespo Patricia, Taboada-Valladares Begoña, Lobato-Busto Ramón, Gómez-Caamaño Antonio, Vega Ana
Grupo Genética en Cáncer y Enfermedades Raras, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Fundación Pública Galega de Medicina Xenómica (FPGMX), 15706 Santiago de Compostela, A Coruña, Spain.
Department of Radiation Oncology Hospital Clínico Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Grupo Genética en Cáncer y Enfermedades Raras, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), 15706 Santiago de Compostela, A Coruña, Spain.
Cancers (Basel). 2021 Mar 22;13(6):1447. doi: 10.3390/cancers13061447.
Several studies have identified single-nucleotide polymorphisms (SNPs) associated with adverse effects in non-small-cell lung cancer (NSCLC) patients treated with radiation therapy. Here, using an independent cohort, we aimed to validate the reported associations. We selected 23 SNPs in 17 genes previously associated with radiation-induced oesophagitis for validation in a cohort of 178 Spanish NSCLC patients. Of them, 18 SNPs were finally analysed, following the methods described in the original published studies. Two SNPs replicated their association with radiation-induced oesophagitis (rs7165790 located in the gene: odds ratio (OR) = 0.16, 95% CI = 0.04-0.65, -value = 0.010; rs4772468 at : OR = 4.36, 95% CI = 1.15-16.46, -value = 0.029). The SNP rs2868371 at was also validated but displayed an opposite effect to the formerly described (OR = 3.72; 95% CI = 1.49-9.25; -value = 0.004). Additionally, we tested a meta-analytic approach including our results and the previous datasets reported in the referenced publications. Twelve SNPs (including the two previously validated) retained their statistically significant association with radiation-induced oesophagitis. This study strengthens the role of inflammation and DNA double-strand break repair pathways in the risk prediction of developing radiation-induced oesophagitis in NSCLC patients. The validated variants are good candidates to be evaluated in risk prediction models for patient stratification based on their radiation susceptibility.
多项研究已确定了与接受放射治疗的非小细胞肺癌（NSCLC）患者不良反应相关的单核苷酸多态性（SNP）。在此，我们使用一个独立队列，旨在验证已报道的相关性。我们在先前与放射性食管炎相关的17个基因中选择了23个SNP，在178名西班牙NSCLC患者队列中进行验证。其中，按照最初发表研究中描述的方法，最终分析了18个SNP。两个SNP重复了它们与放射性食管炎的相关性（位于基因中的rs7165790：比值比（OR）=0.16，95%置信区间（CI）=0.04 - 0.65，P值=0.010；位于的rs4772468：OR = 4.36，95% CI = 1.15 - 16.46，P值=0.029）。位于的SNP rs2868371也得到了验证，但显示出与先前描述的相反效应（OR = 3.72；95% CI = 1.49 - 9.25；P值=0.004）。此外，我们测试了一种荟萃分析方法，将我们的结果与参考文献中报道的先前数据集相结合。12个SNP（包括先前验证的两个）与放射性食管炎保持着统计学上的显著相关性。本研究强化了炎症和DNA双链断裂修复途径在NSCLC患者发生放射性食管炎风险预测中的作用。经过验证的变体是基于患者辐射易感性在风险预测模型中进行评估以实现患者分层的良好候选因素。
