Background: Cancer stem cells are believed to be involved in resistance to radiotherapy and chemotherapy and responsible for local recurrence and distant metastasis.We hypothesized that genetic variations in CD133 (also called PROM1),an important marker gene of cancer stem cells,affect clinical outcomes among patients with non-small cell lung cancer (NSCLC) treated with definitive radiotherapy.Methods: We identified 393 patients with primary NSCLC who had received definitive radiotherapy at asingle institution from March 1998 through February 2009.We genotyped four potentially functional single nucleotide polymorphisms (SNPs) of CD133 (rs2240688A>C,rs10022537A>T,rs7686732G>C,and rs3130T>C) and estimated their associations with local recurrence-free survival (LRFS),distant metastasisfree survival (DMFS),and overall survival (OS) by using Cox proportional hazards models.Results: Only rs2240688 SNPs were associated with LRFS and DMFS after adjustment for patient characteristics.Specifically,patients ith the rs2240688C variant genotypes (AC/CC) had longer LRFS (logrank P=0.048,adjusted hazard ratio [HR] =0.74,95% CI 0.58-0.96,adjusted P=0.023) and DMFS (log-rank P=0.059,adjusted HR=0.76,95% CI 0.59-0.98,adjusted P=0.032) than did patients with the AA genotypes.In stratification analysis,associations of the AC/CC variant genotypes with LRFS,DMFS,and OS were strongest among patients with stage Ⅲ-Ⅳ disease,or those who received <66 Gy in log-rank test and multivariable Cox models analysis.Conclusions: Our findings suggest that rs2240688 SNPs in CD133 may predict prognosis and could be used to optimize treatment strategies for patients with NSCLC.Larger,prospective studies are needed to confirm these findings.