Abstract
BackgroundThe 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.Methodology/Principal FindingsA 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.ConclusionsThe 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.
Highlights
The urothelium is the epithelial lining of the urinary tract from the renal calyces to the bladder
The rs6950683 SNPs of enhancer of zeste homolog 2 (EZH2) might contribute to the prediction of urothelial cell carcinoma (UCC) susceptibility
This is the first study to provide insight into risk factors associated with EZH2 variants in carcinogenesis of UCC in Taiwan
Summary
The urothelium is the epithelial lining of the urinary tract from the renal calyces to the bladder. More than 95% of all bladder cancers are urothelial cell carcinomas (UCC). The majority of UCCs are bladder tumors, whereas upper urinary tract tumors and tumors of the urethra contribute less than 10%. The molecular biology of UCC has been extensively studied in recent years, and many genetic alterations and modified expression patterns of certain oncogenes and tumor suppressor genes have been linked to its tumorigenesis and progression [5]. The gene EZH2, the polycomb group protein enhancer of zeste 2, encodes a transcriptional repressor that 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
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