title: Effects of EZH2 promoter polymorphisms and methylation status on oral squamous cell carcinoma susceptibility and pathology.
abstract: Oral squamous cell carcinoma (OSCC), which is malignant tumors in oral cavity, is the fourth most common male cancer in Taiwan. EZH2 plays a key role in transcriptional repression through chromatin remodeling and in cancer development. Although the EZH2 expression in OSCC is highly correlated with tumorigenesis, it has not been determined if specific EZH2 genetic variants are associated with OSCC risk. The aim of this study was to investigate the relationship between genetic polymorphisms of EZH2 and susceptibility to OSCC in Taiwan. Here, four SNPs of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by a real-time PCR genotyping in 576 patients with oral cancer and 552 cancer-free controls. After adjusting for other co-variants, we found that carrying CC genotype at EZH2 rs6950683 and rs3757441 had a lower risk of developing OSCC than did wild-type carriers. The CCCA or CCTA haplotype among the four EZH2 sites was also associated with a reduced risk of OSCC. Furthermore, OSCC patients who carried CC genotype at EZH2 rs6950683 had a higher methylation than TC genotype. Our results suggest that the two SNPs of EZH2 (rs6950683 and rs3757441) might contribute to the prediction of OSCC susceptibility. Moreover, rs6950683 CC genotype exhibits hypermethylation in EZH2 promoter. This is the first study to provide insight into risk factors associated with EZH2 variants and epigenetic changes in carcinogenesis of OSCC in Taiwan.
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica Taichung, Taiwan.
authors.forename: Kuo-Jung
authors.initials: KJ
authors.lastname: Su
authors.affiliation: Institute of Oral Sciences, Chung Shan Medical UniversityTaichung, Taiwan; Department of Dentistry, Chung Shan Medical University HospitalTaichung, Taiwan.
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Institute of Medicine, Chung Shan Medical UniversityTaichung, Taiwan; Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian HospitalChanghua, Taiwan.
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Institute of Medicine, Chung Shan Medical UniversityTaichung, Taiwan; Department of Medical Research, Chung Shan Medical University HospitalTaichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia SinicaTaichung, Taiwan; Graduate Institute of Cancer Biology, China Medical UniversityTaichung, Taiwan; Center for Molecular Medicine, China Medical University HospitalTaichung, Taiwan; Department of Biotechnology, Asia UniversityTaichung, Taiwan.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
keywords: EZH2; bisulfite sequencing; methylation; oral squamous cell carcinoma; single-nucleotide polymorphism (SNP)