Prognostic value of the TGFβ1 rs4803455 single nucleotide polymorphism in small cell lung cancer

Background: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein beta 1 (HSPB1) and transforming growth factor beta 1 (TGF beta 1) and survival have been investigated. Methods: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGF beta 1 gene and 5 of HSPB1 gene) variables were analyzed. Results: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGF beta 1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17;p=0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5;p= 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83;p= 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p<0.001) and DFS (p<0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. Conclusions: Genetic analysis showed the CA genotype of TGF beta 1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.