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


CONCLUSIONS
Genetic polymorphism of the TGFB1 signal sequence is associated with the response to chemoradiotherapy. TGF-beta1 may sensitize cancer stem cells to chemoradiotherapy.
Lundberg
Marie
M
Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
Pajusto
Mervi
M
Koskinen
Walter J
WJ
Mäkitie
Antti A
AA
Aaltonen
Leena-Maija
LM
Mattila
Petri S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D053773:Transforming Growth Factor beta1