BACKGROUND: The 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 METHODS: We 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. RESULTS: No 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. CONCLUSION: The VHL and HIF1A polymorphisms may not influence RCC susceptibility but may jointly influence RCC progression and survival.
BACKGROUND: The 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 METHODS: We 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. RESULTS: No 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. CONCLUSION: The VHL and HIF1A polymorphisms may not influence RCC susceptibility but may jointly influence RCC progression and survival.
Authors: Xiang Shu; Jianchun Gu; Maosheng Huang; Nizar M Tannir; Surena F Matin; Jose A Karam; Christopher G Wood; Xifeng Wu; Yuanqing Ye Journal: Carcinogenesis Date: 2018-05-28 Impact factor: 4.944