Zhou Yuan, Du Wei-Dong, Wu Qiang, Liu Yi, Chen Gang, Ruan Jian, Xu Song, Yang Feng, Zhou Fu-Sheng, Tang Xian-Fa, Tang Hua-Yang, Zuo Xian-Bo, Zhang Feng-Yu, Sun Liang-Dan, Zhang Xue-Jun
Key Lab of Genome Research of Anhui Province, Anhui Medical University, Hefei, China; Department of Biology, Anhui Medical University, Hefei, China.
Mol Carcinog. 2014 Aug;53(8):589-97. doi: 10.1002/mc.21871. Epub 2012 Jan 6.
Enhancer of zeste 2 (EZH2) gene encodes a histone methyltransferase that constitutes the catalytic component of the polycomb repressive complex-2 (PRC2) to initiate epigenetic silencing of genes. It is reported that the expression level of EZH2 in gastric cancer tissue was highly correlated with tumor progression, however, whether EZH2 genetic variants were associated with the risk of gastric cancer remains yet unknown. In this study, we conducted a genotyping analysis for EZH2 in 311 cases of gastric cancer and 425 controls from the Chinese Han population. We found five single nucleotide polymorphisms (SNP; rs12670401, rs6464926, rs2072407, rs734005, and rs734004) of EZH2 gene were significantly associated with the risk of gastric cancer. Of which, the rs12670401 with the minor allele C and rs6464926 with the minor allele T revealed strong associations with increased gastric cancer risk [P = 0.009, adjusted odds ratio (aOR) = 1.327, 95% CI = 1.075-1.683 and P = 0.012, aOR = 1.310, 95% CI = 1.059-1.619]. The other three SNPs, rs2072407, rs734005, and rs734004 contributed 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 = 0.642-0.995 and P = 0.048, aOR = 0.803, 95% CI = 0.645-0.999), respectively. We further found that rs12670401 and rs6464926 were in a strong LD while rs2072407, rs734005, and rs734004 were in another. Haplotype analysis of the five SNPs showed that haplotype CCTCT reduced the risk of gastric cancer (P = 0.031 and aOR = 0.784), while haplotype GTCTC significantly elevated the risk of gastric cancer (P = 0.011 and aOR = 1.310). We concluded that EZH2 variants were significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of EZH2 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.
zeste 2增强子（EZH2）基因编码一种组蛋白甲基转移酶，该酶构成多梳抑制复合物2（PRC2）的催化成分，从而启动基因的表观遗传沉默。据报道，EZH2在胃癌组织中的表达水平与肿瘤进展高度相关，然而，EZH2基因变异是否与胃癌风险相关仍不清楚。在本研究中，我们对311例中国汉族胃癌患者和425例对照进行了EZH2基因分型分析。我们发现EZH2基因的五个单核苷酸多态性（SNP；rs12670401、rs6464926、rs2072407、rs734005和rs734004）与胃癌风险显著相关。其中，次要等位基因C的rs12670401和次要等位基因T的rs6464926与胃癌风险增加密切相关[P = 0.009，校正比值比（aOR）= 1.327，95%置信区间（CI）= 1.075 - 1.683；P = 0.012，aOR = 1.310，95% CI = 1.059 - 1.619]。另外三个SNP，rs2072407、rs734005和rs734004则显著降低了胃癌风险（P = 0.033，aOR = 0.787，95% CI = 0.633 - 0.981；P = 0.045，aOR = 0.799，95% CI = 0.642 - 0.995；P = 0.048，aOR = 0.803，95% CI = 0.645 - 0.999）。我们进一步发现rs12670401和rs6464926处于强连锁不平衡状态，而rs2072407、rs734005和rs734004处于另一种连锁不平衡状态。对这五个SNP的单倍型分析表明，单倍型CCTCT降低了胃癌风险（P = 0.031，aOR = 0.784），而单倍型GTCTC则显著增加了胃癌风险（P = 0.011，aOR = 1.310）。我们得出结论，EZH2变异与胃癌风险显著相关。我们的结果首次为中国汉族人群胃癌发生过程中EZH2基因变异的易感因素提供了新的见解。
