Intronic variant of EGFR is associated with GBAS expression and survival outcome of early-stage non-small cell lung cancer

Background: Genome-wide association studies have indicated that most of the currently identified disease and trait-associated single nucleotide polymorphisms(SNPs) are intronic or intergenic. RegulomeDB is a recently developed database that provides functional annotations for regulatory features of SNPs located in non-coding regions. We evaluated the potential regulatory SNPs in the EGFR gene region using RegulomeDB and their associations with prognosis after surgery in non-small cell lung cancer (NSCLC) patients. Methods: A total of 698 patients with surgically resected NSCLC were enrolled and seven SNPs were selected based on the RegulomeDB database. All SNPs were genotyped using SEQUENOM MassARRAY iPLEX assay. Results: Among the seven SNPs evaluated, rs9642391 (EGFR ivs19+2851C＞G) was significantly associated with survival outcome (adjusted hazard ratio [HR] for overall survival=0.70, 95% confidence interval [CI] 0.56-0.87, P=0.001; adjusted HR for disease-free survival=0.82, 95% CI 0.70-0.97, P=0.02; under a codominant model). According to RegulomeDB, rs9642391C＞G, which is located in intron 19 of EGFR, was predicted to influence the expression of GBAS but not EGFR. As predicted, rs9642391C＞G was associated with GBAS (P=0.024) but not EGFR messenger RNA expression in tumor tissues. Conclusion: In conclusion, our study provides evidence that rs9642391C＞G in the intron of EGFR is associated with GBAS expression and survival outcomes of patients with surgically resected early-stage NSCLC.