title: Impact of EZH2 polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic features.
abstract: BACKGROUND
  The gene EZH2, the polycomb group protein enhancer of zeste 2, encodes a transcriptional repressor that also serves as a histone methyltransferase that is associated with progression to more advanced disease in a variety of malignancies. EZH2 expression level in urothelial cell carcinoma (UCC) is highly correlated with tumor aggressiveness, but it has not been determined if specific EZH2 genetic variants are associated with UCC risk. This study investigated the potential associations of EZH2 single-nucleotide polymorphisms with UCC susceptibility and its clinicopathologic characteristics.
  
  
  RESULTS
  A total of 233 UCC patients and 552 cancer-free controls, all of whom were from Taiwan, were analyzed for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441, and rs41277434) using real-time PCR genotyping. After adjusting for other co-variants, we found that individuals carrying at least one C allele at EZH2 rs6950683 had a lower risk of developing UCC than did major allele carriers. The CCCA or TGTA haplotype among the four EZH2 sites was also associated with a reduced risk of UCC. Furthermore, UCC patients who carried at least one G allele at rs2302427 had a lower invasive tumor stage than did patients carrying the major allele.
  
  
  CONCLUSIONS
  The rs6950683 SNPs of EZH2 might contribute to the prediction of UCC susceptibility. This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of UCC in Taiwan.
authors.affiliation: Graduate Institute of Cancer Biology, and Center for Molecular Medicine, China Medical University, Taichung, Taiwan; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan.
authors.forename: Kuo-Jung
authors.initials: KJ
authors.lastname: Su
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shian-Shiang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Wang
authors.affiliation: Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Weng
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2