ASSOCIATION BETWEEN TRANSFORMING GROWTH FACTOR beta 1 GENETIC POLYMORPHISM AND RESPONSE TO CHEMORADIOTHERAPY IN HEAD AND NECK SQUAMOUS CELL CANCER

作者：Lundberg Marie; Pajusto Mervi; Koskinen Walter J; Makitie Antti A; Aaltonen Leena Maija; Mattila Petri S^*

来源：Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, 2009, 31(5): 664-672.

DOI：10.1002/21014

• head and neck squamous cell carcinoma
• transforming growth factor beta
• genetic polymorphism
• radiotherapy
• neoplastic stem cells

Background. Transforming growth factor beta (TGF-beta) is a pleiotropic cytokine that has diverse roles in cancer. Rate of production of the major isoform, TGF-beta 1, is linked with rs1982073 single nucleotide polymorphism in TGF-beta 1 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 TGF beta 1 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% Cl 1.12-10.5 and 3.09, 95% CI 0.96-10.0, respectively).
Conclusion. Genetic polymorphism of the TGF-beta 1 signal sequence is associated with the response to chemoradiotherapy. TGF-beta 1 may sensitize cancer stem cells to chemoradiotherapy.

• 出版日期2009-5