title: The Clinicopathological Significance of Epigenetic Silencing of VHL Promoter and Renal Cell Carcinoma: A Meta-Analysis.
abstract: OBJECTIVE
  Von Hippel-Lindau gene (VHL) has been reported as a tumor-suppressor gene in some cancers. However, the association between VHL promoter hypermethylation and renal cell carcinoma (RCC) remains to be clarified. We are the first to systematically integrate published papers to assess the role of hypermethylated VHL in RCC.
  
  
  METHODS
  The potential relevant papers were searched via PubMed, Embase, EBSCO, CNKI, and Wanfang databases. The overall odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to evaluate the relationship between VHL promoter hypermethylation and RCC.
  
  
  RESULTS
  Finally, a total of 1,998 RCC patients and 294 controls from 13 eligible articles were included in this meta-analysis. Under the fixed-effects model, the pooled OR from seven studies including 596 RCC and 294 nonmalignant samples showed that VHL promoter hypermethylation was significantly higher in cancer than in controls (OR = 7.93, 95% CI = 2.84- 22.15, P < 0.001). Subgroup analysis based on ethnic population and testing method revealed that hypermethylated VHL had a significantly similar OR value in different races and detection methodologies. No significant association was found between hypermethylated VHL and tumor grade, tumor stage, tumor size, histological types, and lymph node status in cancer (all P > 0.05). In the current study, there was no evidence of publication bias as determined by Egger's test (all P > 0.05).
  
  
  CONCLUSIONS
  In the investigated patients, VHL promoter hypermethylation, which may play an important role in carcinogenesis of RCC, is significantly associated with an increased risk of RCC. However, VHL promoter hypermethylation is not correlated with specific clinicopathological characteristics. Additional future studies are needed to confirm our results.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Zhao
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Cong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D011401:Promoter Regions, Genetic; D017594:Publication Bias; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human