Polymorphisms of HIF1A gene are associated with prognosis of early stage non-small-cell lung cancer patients after surgery

Hypoxia- inducible factor 1 alpha a (HIF1 alpha) activates the transcription of genes that are involved in angiogenesis and cell survival. Over- expression of HIF1 alpha caused by intratumoral hypoxia and its genetic alterations are associated with increased mortality in several cancer types including non- small- cell lung cancer (NSCLC). The aim of this study was to investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in NSCLC outcomes. We genotyped two functional SNPs (rs2057482 and rs2301113) in HIF1A gene and assessed their associations with clinicopathological parameters and prognosis of 494 NSCLC patients by Cox proportional hazard model. There was no significant association between the SNPs and clinical outcomes of NSCLC for overall analysis. However, in stratified analysis for NSCLC patients at early stage (I/ II), we observed a protective effect conferred by variant genotype of rs2057482 on overall survival (OS) (HR 0.42, 95 % CI 0.22- 0.80) and recurrence- free survival (RFS) (HR 0.60, 95 % CI 0.36- 0.97) in a dominant model. Additionally, multivariate Cox analysis based on dominant model indicated that significant increased death and recurrence risks were observed in patients with early T- stage (T1 and T2) tumors, who carrying variant- containing genotype of rs2301113, as well as in patients without lymph node involvement (N0 stage) for rs2057482. Genetic variations on HIF1A gene are significantly associated with NSCLC outcomes in patients with early stage disease.