We, therefore, performed a case-control study of four SNPs located in the promoter, exonic, and intronic regions of EZH2 to assess the associations between these SNPs and HCC susceptibility and clinicopathologic characteristics. The major etiologies for HCC in Taiwan include infection with HBV or HCV, alcohol consumption, history of liver cirrhosis, and family history of HCC. In our HCC group, however, alcohol consumption and tobacco use were not significantly different from those of healthy controls, suggesting that these two risk factors alone do not fully explain the pathogenesis of HCC and that genetic components may play a pivotal role. This is consistent with the observations that many gene polymorphisms and somatic mutations have been associated with the preneoplastic stage of HCC. We observed that at least one polymorphic C allele at SNPs rs6950683 and rs3757441 is strongly associated with reduced HCC risk. Rs3757441 is an intronic SNP, and as such may affect gene expression through several mechanisms, including changes in transcription�Cfactor binding sites, microRNA-targeting sequences, and splicing variants. Rs6950683, is located upstream of exon 1, and, therefore, may impact gene expression by affecting promoter function. Further functional studies are AbMole Metaproterenol Sulfate needed to confirm the specific mechanisms by which these EZH2 polymorphisms influence the development of HCC. Although the functional importance of rs6950683 and rs3757441 has not been tested experimentally, it has been observed that individuals carrying C/C alleles at these two SNPs have a lower risk of lung cancer than do those carrying the T/T wild-type allele. This study provides novel information on the effects of single nucleotide polymorphisms in EZH2 on HCC susceptibility and clinicopathology, but found that HCC patients carrying rs6950683 and rs3757441 polymorphisms have a higher risk of lymph node metastasis than wild-type carriers. However, the number of individuals examined in this study was relatively small, and additional studies with more patients are needed to verify the effects of EZH2 polymorphisms on HCC that we observed and to explore the effects of these variants on the biological function of EZH2. Although many SNPs have no direct effect on gene products, they can still be used as genetic markers to locate adjacent functional variants that contribute to disease. In addition, the contribution of SNPs to a disease-related haplotype may not be apparent when looking at individual SNPs. Therefore, haplotype analysis is sometimes advantageous over analysis of individual SNPs for detecting an association between alleles and a disease phenotype. Our haplotype analysis of the four EZH2 SNPs rs6950683, rs2302427, rs3757441, and rs41277434 revealed 
that the CCCA and CCTA haplotypes are associated with a lower risk of HCC. However, it is possible that these EZH2 SNPs are linked with other functional polymorphisms and are, therefore, not directly responsible for the decreased susceptibility to HCC. In conclusion, this is the first study to show a significant association between polymorphisms in EZH2 and HCC risk. These findings suggest that the presence of a variant EZH2 allele may be a protective factor for the development of HCC and could be a useful genetic marker for predicting susceptibility to HCC. Communication between nerve cells in the brain can simplistically be described as a biochemical concert of synaptic neurotransmitters, receptors, ion channels and effector molecules, coding and controlling signal AbMole (R)-(-)-Modafinic acid transmission. Regulation of signaling efficiency is basically controlled by down-stream regulating molecular system that modulates synaptic transmission.