| Purposes To investigate associations between genetic variants in Enhancer ofZeste Homolog2(EZH2) genes and risk of gastric cancer.Methods In this study, we conducted a genotyping analysis for EZH2in311cases of gastric cancer and425controls from the Chinese Han population. Inaddition, we examined EZH2expression in238gastric cancer tissues and theircorresponding non-cancerous gastric mucosa by TMA and IHC.Results We found five SNP polymorphisms (rs12670401, rs6464926,rs2072407, rs734005and rs734004) of EZH2gene were significantlyassociated with the risk of gastric cancer. Of which, the rs12670401with theminor allele C and rs6464926with the minor allele T revealed strongassociations with increased gastric cancer risk [P=0.009, adjusted OR(aOR)=1.327,95%CI=1.075-1.683and P=0.012, aOR=1.310,95%CI=1.059-1.619]. The other three SNPs, rs2072407, rs734005andrs734004contributed to significantly reduced risk of gastric cancer (P=0.033,aOR=0.787,95%CI=0.633-0.981, P=0.045, aOR=0.799,95%CI=0.642-0.995and P=0.048, aOR=0.803,95%CI=0.645-0.999), respectively. We further foundthat rs12670401and rs6464926were in a strong LD while rs2072407,rs734005and rs734004were in another. Haplotype analysis of the five SNPsshowed that haplotype CCTCT reduced the risk of gastric cancer (P=0.031andaOR=0.784), while haplotype GTCTC significantly elevated the risk of gastriccancer (P=0.011and aOR=1.310). We found that faint EZH2immunoreactivity was restricted to the nuclei of epithelial cells of non-cancerous gastric mucosa.Similarly, individual subtypes of gastric cancer represented EZH2-specificsignals in nuclei (Figure2a-f). No cytoplasmic staining of gastric cancer wasobserved. Neither significant immunoreactivity difference of EZH2amonggastric cancer tissues nor correlations between EZH2expression and clinicpathological factors were found (data not shown)Conclusion We concluded that EZH2variants were significantly associatedwith gastric cancer risk. Our results for the first time provided new insight intosusceptibility factors of EZH2gene variants in carcinogenesis of gastric cancer Purposes To investigate associations between genetic variants involved inmicroRNA networks (microRNA biogenesis, microRNA and microRNA bindingsites) and risk of gastric cancer.Methods We genotyped19SNPs of the microRNA related genes in acase-control study of311gastric cancers and425cancer-free controls in aChinese Han population.Results We found that two of the SNPs were significantly associated with gastriccancer. Inhibitory effect of minor allele T of rs2071504SNP within the exon ofPOLR2A gene was significantly associated with gastric carcinogenesis (P=0.033,aOR=0.742,95%CI=0.564-0.977) and the SNP rs895819in the miR-27a genewith the minor allele C presented significantly reduced risk to gastric cancer(P=0.037, aOR=0.771,95%CI=0.604-0.985). Further stratified analysis withregard to clinical pathological parameters of the patients indicated that the SNPrs2071504was associated with lymph node metastasis (P=0.021, aOR=0.529,95%CI=0.307-0.910) and TMN stage (P=0.021, aOR=0.532,95%CI=0.311-0.908), respectively.Conclusions Our findings provided evidence that the SNP rs2071504in theexon of POLR2A gene would not only confer a decreased risk of gastric cancer,but also influence lymph node metastasis and TMN stage of gastric cancer in theChinese population... |
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