RESUMEN
BACKGROUND AND PURPOSE: Radiochemotherapy (RCT) success in lung cancer (LC) can be limited due to the onset of adverse effects in the adjacent normal tissue such as radiation-induced esophageal toxicity (RIET). Therefore, specific biomarkers to customize the RCT dose administration and esophageal toxicity prediction are necessary to improve treatment effectiveness. MATERIALS AND METHODS: 247 LC patients prospectively recruited between 2012 and 2016 from 3 institutions were genotyped for 7 SNPs along TGFB1 and HSPB1 genes seeking an association with RIET risk development. Kaplan-Meier cumulative probability and Cox proportional hazards analyses were used to evaluate the effect of TGFB1 and HSPB1 genotypes on such risk. RESULTS: Multivariate analyses showed that patients carrying the HSPB1 rs7459185 CC genotype were associated with a significantly higher risk of acute grade 3 RIET than those carrying the GG/GC genotypes (HRâ¯=â¯17.73; 95% CIâ¯=â¯2.896-108.49; pâ¯=â¯0.002). LC patients who received higher (>median) volume of esophagus exposed to 30â¯Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (pâ¯<â¯0.001). Additionally, LC patients carrying the TGFB1 rs11466353 GG genotype were found to be associated with a lower risk of late grade 2 RIET compared with those with the TT/TG genotypes (HRâ¯=â¯0.29; 95% CIâ¯=â¯0.103-0.830; pâ¯=â¯0.021). Patients receiving a high (>60â¯Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (pâ¯=â¯0.025). CONCLUSION: The presence of different rs7459185/rs11466353 genotypes in LC patients associated with RIET risk and may be useful biomarkers along with other risk factors for guiding therapy intensity in an individualized therapy.