Regulatory variants in cancer-related pathway genes predict survival of patients with surgically resected non-small cell lung cancer

Background We conducted this study to identify genetic variants in cancer-related pathway genes which can predict prognosis of NSCLC patients after surgery, using a comprehensive list of regulatory single nucleotide polymorphisms (SNPs) prioritized by RegulomeDB. Method A total of 509 potentially functional SNPs in cancer-related pathway genes selected from RegulomeDB were evaluated. These SNPs were analyzed in a discovery set (n = 354), and a replication study was performed in an independent set (n = 772). The association of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. Results In the discovery set, 76 SNPs were significantly associated with OS or DFS. Among the 76 SNPs, the association was consistently observed for 5 SNPs (ERCC1 rs2298881C > A, BRCA2 rs3092989G > A, NELFE rs440454C > T, PPP2R4 rs2541164G > A, and LTBP4 rs3786527G > A) in the validation set. In combined analysis, ERCC1 rs2298881C > A, BRCA2 rs3092989, NELFE rs440454C > T, and PPP2R4 rs2541164G > A were significantly associated with OS and DFS (adjusted HR ·aHR· for OS = 1.46, 0.62, 078, and 0.76, respectively; P = 0.003, 0.002, 0.007, and 0.003 respectively; and aHR for DFS = 1.27, 0.69, 0.86, and 0.82, respectively; P = 0.02, 0.002, 0.03, and 0.008, respectively). The LTBP4 rs3786527G > A was significantly associated with better OS (aHR = 0.75; P = 0.003). Conclusion Our results suggest that five SNPs in the cancer-related pathway genes may be useful for the prediction of the prognosis in patients with surgically resected NSCLC.