Prognostic Significance of Telomerase Polymorphism in Non-Small Cell Lung Cancer

Purpose: Lung cancer is the leading cause of death in oncologic patients of western countries, with very low survival rates. Telomerase main components are the catalytic subunit (hTERT) and the RNA template (hTR). A functional polymorphism in the hTERT gene was found in the promoter region (-1327T/C), and individuals homozygous for the -1327C/C genotype present shorter telomere length compared with T-carrier genotypes. Our purpose was to investigate the potential prognostic role of the hTERT functional genetic variant in non-small cell lung cancer (NSCLC) patients. Experimental Design: We prospectively conducted a study involving 226 patients with NSCLC treated with a first-line chemotherapeutic standard protocol. A follow-up study was undertaken (median follow-up time, 26 months) to evaluate treatment response and overall survival of NSCLC patients. The hTERT -1327T/C genetic variants were analyzed by allelic discrimination with real-time PCR. Results: Our results indicate an influence of the telomerase genetic variants in the overall survival of NSCLC patients. Cox regression analysis showed a significantly higher median estimated cumulative survival of 26.5 months in T-carrier patients, compared with that of 19.3 months in CC patients (hazard ratio, 0.52; 95% confidence interval, 0.35-0.77; P = 0.001). Conclusions: Telomerase functional polymorphism in the hTERT gene may contribute as a prognostic factor in NSCLC patients. Our findings indicate that hTERT genetic variants, by modulating telomere length, may confer an advantage in chemotherapy response. The assessment of telomerase genetic variants could supplement prognosis of survival in the course of NSCLC and may be a promising molecular marker of treatment response in these patients. Clin Cancer Res; 16(14); 3706-12. (C)2010 AACR.