The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cell carcinoma

BackgroundThe von Hippel–Lindau (VHL) tumor suppressor gene and hypoxia-inducible factor-1α (HIF1A) play a pivotal role in renal carcinogenesis. This study was aimed to clarify the influence of VHL and HIF1A polymorphisms on renal cell cancer (RCC) susceptibility and survival.Subjects and methodsWe genotyped four potentially functional single-nucleotide polymorphisms (rs779805 in VHL and rs11549465, rs11549467, and rs2057482 in HIF1A) and assessed their associations with RCC risk, clinicopathologic parameters in a case–control study of 620 patients and 623 controls, and the prognosis of RCC in a cohort of 311 patients.ResultsNo significant differences in VHL or HIF1A genotypes were observed between RCC cases and controls. However, individuals with ≥2 variant alleles of the four polymorphisms were associated with less frequent lymph node metastasis and lower clinical stage (P = 0.032 and P = 0.041, respectively). And the number of variant alleles was associated with improved survival in a dose–response manner (P_trend = 0.013). Furthermore, multivariate Cox regression analysis showed that the number of variant alleles (≥1 versus 0) was an independent prognostic factor for RCC survival (P = 0.036) together with clinical stage and tumor grade.ConclusionThe VHL and HIF1A polymorphisms may not influence RCC susceptibility but may jointly influence RCC progression and survival.