Association between transforming growth factor β1 genetic polymorphism and response to chemoradiotherapy in head and neck squamous cell cancer

Abstract

Background. Transforming growth factor β (TGF-β) is a pleiotropic cytokine that has diverse roles in cancer. Rate of production of the major isoform, TGF-β1, is linked with rs1982073 single nucleotide polymorphism in TGFB1 gene signal sequence. Methods. 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. Results. 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). Conclusion. Genetic polymorphism of the TGFB1 signal sequence is associated with the response to chemoradiotherapy. TGF-β1 may sensitize cancer stem cells to chemoradiotherapy. © 2009 Wiley Periodicals, Inc.