Association between transforming growth factor beta1 genetic polymorphism and response to chemoradiotherapy in head and neck squamous cell cancer.

Abstract

Transforming growth factor beta (TGF-beta) is a pleiotropic cytokine that has diverse roles in cancer. Rate of production of the major isoform, TGF-beta1, is linked with rs1982073 single nucleotide polymorphism in TGFB1 gene signal sequence. Peripheral blood DNA of 175 head and neck squamous cell carcinoma patients were genotyped using real-time PCR and fluorescent probes. The median follow-up time was 2.9 years (range, 0.1-15.9 years). Survival was assessed using Cox regression. Among the 38 patients who had received chemoradiotherapy without surgical resection the high-producer TGFB1 genotypes CC and CT were associated with a better disease-free and overall survival when compared with the low-producer TT genotype (hazard ratios for interaction 3.42, 95% CI 1.12-10.5 and 3.09, 95% CI 0.96-10.0, respectively). Genetic polymorphism of the TGFB1 signal sequence is associated with the response to chemoradiotherapy. TGF-beta1 may sensitize cancer stem cells to chemoradiotherapy.