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

被引：53
作者：
Qin, C. [1 ]
Cao, Q. [1 ]
Ju, X. [1 ]
Wang, M. [2 ]
Meng, X. [1 ]
Zhu, J. [1 ]
Yan, F. [2 ]
Li, P. [1 ]
Ding, Q. [1 ]
Chen, J. [1 ]
Gu, M. [1 ]
Zhang, W. [1 ]
Yin, C. [1 ]
Zhang, Z. [2 ,3 ]
机构：
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Sch Publ Hlth, Dept Mol & Genet Toxicol, Nanjing 210029, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Sch Publ Hlth, Dept Occupat Med & Environm Hlth,Canc Ctr, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 210029, Jiangsu, Peoples R China
来源：
ANNALS OF ONCOLOGY | 2012年 / 23卷 / 04期
关键词：
HIF1A; polymorphism; prognosis; renal cell carcinoma; VHL; INDUCIBLE FACTOR-1-ALPHA GENE; ENDOTHELIAL GROWTH-FACTOR; FACTOR; 1-ALPHA; PROSTATE-CANCER; RISK; SUSCEPTIBILITY; HIF-1-ALPHA; SURVIVAL; PROLIFERATION; EXPRESSION;
D O I：
10.1093/annonc/mdr325
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: The von Hippel-Lindau (VHL) tumor suppressor gene and hypoxia-inducible factor-1 alpha (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.
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页码：981 / 989
页数：9
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