Imaging, Diagnosis, Prognosis A Polymorphic 844T/C in FasL Promoter Predicts Survival and Relapse in Non–Small Cell Lung Cancer

Purpose: Fas ligand (FasL) 844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL 844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL 844T/C polymorphism on the clinical outcome of non–small cell lung cancer (NSCLC) remains to be identified. Experimental Design: A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL 844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL 844T/C polymorphism on survival and relapse was determined by Kaplan–Meier analysis and Cox proportional hazards models. Results: The FasL 844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P 1⁄4 0.008). In addition, patients with the FasL 844CC genotype were more prone to tumor relapse than those with the FasL 844TTþTC genotype (62.1% vs. 37.9%, P 1⁄4 0.001). Multivariate Cox regression analysis showed that patients with the FasL 844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL 844TTþTC genotype (24.1 vs. 42.8 months for OS, HR 1⁄4 1.455, P 1⁄4 0.004; 15.4 vs. 31.4 months for RFS, HR 1⁄4 1.710, P < 0.001). Conclusions: FasL 844T/C polymorphismmay predict survival and relapse in NSCLC.We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group. Clin Cancer Res; 17(18); 5991–9. 2011 AACR.