Impact of EZH2 polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic features

• Published in: PloS one Vol. 9; no. 4; p. e93635
• Main Authors: Yu, Yung-Luen, Su, Kuo-Jung, Hsieh, Ming-Ju, Wang, Shian-Shiang, Wang, Po-Hui, Weng, Wei-Chun, Yang, Shun-Fa
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Alleles; Analysis; Biology; Biology and Life Sciences; Bladder; Bladder cancer; Breast cancer; Cancer; Carcinogenesis; Carcinogens; Carcinoma, Transitional Cell - genetics; Carcinoma, Transitional Cell - pathology; Care and treatment; Cell cycle; Cytokines; Deoxyribonucleic acid; Diagnosis; DNA; DNA methylation; Enhancer of Zeste Homolog 2 Protein; Epigenetics; Female; Genes; Genetic Association Studies; Genetic diversity; Genetic polymorphisms; Genetic Predisposition to Disease; Genetic variance; Genotype; Genotyping; Haplotypes; Histone methyltransferase; Histones; Hospitals; Humans; Immunotherapy; Invasiveness; Lung cancer; Male; Medical research; Medicine; Medicine and Health Sciences; Metastasis; Middle Aged; Patients; Polycomb group proteins; Polycomb Repressive Complex 2 - genetics; Polymorphism, Single Nucleotide; R&D; Research & development; Risk analysis; Risk factors; Single-nucleotide polymorphism; Smoking; Taiwan; Transcription; Tumors; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; Urogenital system; Urology; Urothelium - pathology; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093635

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. 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. 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.