Validation of Polymorphisms Associated with the Risk of Radiation-Induced Oesophagitis in an Independent Cohort of Non-Small-Cell Lung Cancer Patients.

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 BLM gene: odds ratio (OR) = 0.16, 95% CI = 0.04-0.65, p-value = 0.010; rs4772468 at FGF14: OR = 4.36, 95% CI = 1.15-16.46, p-value = 0.029). The SNP rs2868371 at HSPB1 was also validated but displayed an opposite effect to the formerly described (OR = 3.72; 95% CI = 1.49-9.25; p-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.