Association of single nucleotide polymorphisms at HSPB1 rs7459185 and TGFB1 rs11466353 with radiation esophagitis in lung cancer

Abstract

[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] 47 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 (HR = 17.73; 95% CI = 2.896–108.49; p = 0.002). LC patients who received higher (>median) volume of esophagus exposed to 30 Gy and harboring the rs7459185 GG/GC genotypes showed a significantly lower RIET incidence (p < 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 (HR = 0.29; 95% CI = 0.103–0.830; p = 0.021). Patients receiving a high (>60 Gy) radiation dose who presented the rs11466353 GG genotype had a significantly lower RIET incidence (p = 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.