EZH2基因多态性与中国女性乳腺癌易感性的分析  

The relevance of EZH2 polymorphism to breast cancer risk in Chinese females:results from a multicenter case-control study

作　　者：赵林枫 于理想[1] 郑超 黄淑亚 刘丽媛[1] 相玉娟 王斐[1] 周飞[1] 周文重 叶春淼 李亮[1] 马忠兵[1] 张强[1] 傅勤烨[1] 余之刚[1] Zhao Linfeng;Yu Lixiang;Zheng Chao;Huang Shuya;Liu Liyuan;Xiang Yujuan;Wang Fei;Zhou Fei;Zhou Wenzhong;Ye Chunmiao;Li Liang;Ma Zhongbing;Zhang Qiang;Fu Qinye;Yu Zhigang(Department of Breast Surgery,the Second Hospital,Cheeloo College of Medicine,Shandong University,Ji'nan 250033,China)

机构地区：[1]山东大学第二医院乳腺外科,济南250033

出　　处：《中华普通外科杂志》2022年第7期508-513,共6页Chinese Journal of General Surgery

基　　金：国家自然科学基金(82072914,81702603);山东省自然科学基金培养基金(ZR2019PH016);国家重点研发计划(2016YFC0901300)。

摘　　要：目的探讨Zeste同源物增强子2(EZH2)基因的单核苷酸多态性(SNPs)与乳腺癌发生风险之间的关系。方法纳入在全国22家三级甲等医院就诊的1039例乳腺癌患者和1040例对照者。检测3个EZH2基因SNPs位点(rs2302427 C>G、rs12670401 T>C和rs6464926 C>T)的基因型分布情况以及不同基因型与乳腺癌发生风险的相关性。使用数据库乳腺癌数据分析EZH2在乳腺癌组织中的表达情况及其与患者预后的关系。结果EZH2 rs6464926 CC基因型与TT基因型(OR=1.362,P=0.015)和显性模型(OR=1.22,P=0.045)乳腺癌发病风险相比差异具有统计学意义。亚组分析表明,在BMI≥24 kg/m^(2)的女性中,与野生型相比,rs6464926位点TC基因型(P=0.050)、TT基因型(P=0.025)和显性模型(TC+TT,P=0.021)患乳腺癌风险差异具有统计学意义。rs6464926位点与EZH2基因表达具有相关性(P=6.89E-47)。EZH2基因在乳腺癌组织中高表达(P<0.001),并且EZH2基因高表达的患者预后与较短的总生存期(HR=1.27,P=0.013)、无远处转移生存期(HR=1.37,P<0.01)和无复发生存期(HR=1.44,P<0.01)相关。结论EZH2 rs6464926多态性位点与中国女性乳腺癌易感性有关,其可能通过影响EZH2表达参与影响乳腺癌的发生和预后。Objective To investigate the relationship between single nucleotide polymorphism(SNPs)of Zeste homolog enhancer 2(EZH2)gene and the risk of breast cancer.Methods Recruiting 1039 breast cancer patients and 1040 controls at 22 referral hospitals nationwide in China,the genotype distribution of 3 SNPs loci of EZH2 genes was observed to detect the correlation between different genotypes and the risk of breast cancer genotypes EZH2 expression in breast cancer tissues and its correlation with patient prognosis were analyzed using breast cancer data from the database.Results EZH2 rs6464926 CC genotype was compared with TT genotype(TT vs.CC:OR=1.362,95%CI:1.063-1.746,P=0.015)and dominant model(TC+TT vs.CC:OR=1.22,95%CI:1.004-1.483,P=0.045).In women with BMI≥24 kg/m^(2),the TC genotype(P=0.050),TT genotype(P=0.025)and dominant model(TC+TT,P=0.021)of rs6464926 locus were significantly different from CC genotype in cancer risk.rs6464926 was correlated with EZH2 gene expression(P=6.89E-47).EZH2 gene is highly expressed in breast cancer tissues,and patients with high expression were associated with shorter OS(HR=1.27,P=0.013),DMFS(HR=1.37,P<0.01),and RFS(HR=1.44,P<0.01).Conclusions The polymorphism rs6464926 of EZH2 gene is associated with breast cancer susceptibility in Chinese women.rs6464926 might regulate breast cancer risk and prognosis by changing EZH2 expression.

关 键 词：乳腺肿瘤 疾病易感性 预后 基因多态性 

分 类 号：R737.9[医药卫生—肿瘤]