Malfunctions of RGS proteins have been reported to be related to the pathogenesis of many common human diseases and drug addiction . Multiple RGS proteins were found differentially expressed in a variety of solid and GANT61 hematological malignancies . The single nucleotide polymorphisms of RGS have been associated with several human diseases, suggesting that genetic variation in the RGS pathway may play a significant role in these diseases�� pathogenesis . Recently, RGS SNPs have also been reported to play important roles in lung cancer. For instance, SNPs in RGS17 on chromosome 6q23-25 was associated with familial lung cancer susceptibility . SNPs in RGS2 and RGS6 may modulate the risks of bladder and lung cancers . Whether genetic variants in the RGS pathway could influence clinical outcomes in patients with NSCLC remains unknown. In this study, we tested the hypothesis that genetic variations of RGS are associated with the survival of late-stage NSCLC patients receiving chemotherapy or chemoradiation. In this study, we found that genetic variations in RGS genes were associated with overall survival in late-stage NSCLC patients. Our findings also reinforced the importance of evaluating the cumulative and interaction effects of genetic variations when predicting clinical outcomes of patients with NSCLC. NSCLC patients are mostly treated with the platinum-based chemotherapy, often in combination with radiation therapy. The platinum-based chemotherapy may be related to several cellular pathways, such as the DNA damage/Abmole Nutlin-3 repair, cell cycle control, and apoptosis pathways . However, there has been no study reporting that RGS is involved in the platinum-based chemotherapy related pathways. NSCLC cells can invade adjacent tissues and metastasize to nonadjacent organs and tissues, processes that may be attributed to altered cellular signaling pathways . Oncogenic transformation is often the direct result of mutations of the signaling molecules, which constitute these pathways. In this study, 5 SNPs were associated with the overall risk of death with bootstrap P values ,0.05 at least 90 times out of 100 times. Three of these 5 SNPs, rs6678136 , rs3820487 and rs2749786 conferred significantly different MST in Kaplan-Meier curve . Previous studies reported that RGS4 gene expression were associated with invasion of several cancer .