title: The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis.
abstract: OBJECTIVE
  Many scientific evidences suggested that the methylation of p16INK4a (p16) was associated with bladder cancer, but some existing studies have yielded inconclusive results about the relationship between p16 promoter methylation and pathological features or the tumor grade of bladder cancer. This meta-analysis of studies aims to evaluate the clinical and prognostic significance of p16 methylation in bladder carcinogenesis.
  
  
  METHODS
  Studies were systemically searched via PubMed and Google Scholar in English up to Sept 2015 and a total of ten appropriate studies (693 cases and 290 controls) with an average NOS score of 6.8 were included. The quality of the appropriate studies was measured by the Newcastle-Ottawa Scale (NOS) assessment.
  
  
  RESULTS
  The meta-analysis results revealed that the methylation state of p16 was statistically significantly associated with an increased risk of bladder cancer (OR=6.71, 95% CI=3.79-11.87) compared to control, and there is no statistically significantly association between the p16 methylation and the tumor pTNM staging (OR=0.59, 95% CI=0.22-1.60) or the tumor grade (OR=1.01, 95% CI=0.52-1.94) in p16 methylated patients compared to unmethylated patients.
  
  
  CONCLUSIONS
  our meta-analysis indicates that p16 promoter methylation may be a promising biomarker for the diagnosis of bladder cancer and the inactivation of p16 may be an early event in bladder carcinogenesis. More studies with larger numbers of participants worldwide are needed to further identify the obvious association above.
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Qi
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Mengxi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology Kangda Road 1#, Haizhu District, Guangzhou 510230, Guangdong, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Que
authors.affiliation: The First Affiliated Hospital, Center for Translational Medicine, Sun Yat-sen University Guangzhou, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
keywords: bladder cancer; meta-analysis; methylation; p16