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

SIMPLE SUMMARY: Genetic variants identified in association with radiation therapy side effects in non-small-cell lung cancer patients require an independent validation. Therefore, the aim of our study was to replicate, in an independent cohort, the analyses of previously published studies associating single-nucleotide polymorphisms with radiation-induced oesophagitis. Following the original models, 2 of the 18 variants associated with radiation-induced oesophagitis in non-small-cell lung cancer patients were confirmed. Furthermore, we meta-analysed our cohort together with those of the reference studies. Twelve variants located in genes of inflammation and DNA double-strand break repair pathways remained associated with oesophagitis. These variants could be included in models for clinical prediction of radiation-induced oesophagitis to evaluate their performance. ABSTRACT: 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.