Chen Li, Liang Yan, Qiu Juhui, Zhang Lingling, Chen Xianchun, Luo Xiangdong, Jiang Jun
J Biomed Sci. 2013 May 28;20(1):32. doi: 10.1186/1423-0127-20-32.
To characterize single nucleotide polymorphisms (SNPs) within the promoter region of the estrogen receptor beta (ERβ) gene and to analyze the association of ERβ SNPs with susceptibility to breast cancer. Genotype frequencies of five SNPs (rs3020449, rs3020450, rs2987983, rs1271572 and rs1887994) in the promoter region of the ERβ gene in 873 women with breast cancer, 645 women with fibroadenoma and 700 healthy women were determined using an allele-specific tetra-primer polymerase chain reaction (PCR). Kaplan-Meier survival analysis was performed to evaluate the association of selected rs1271572 with prognosis in breast cancer. Electrophoretic mobility-shift assays were conducted to explore the binding of SNP rs1271572 containing probes to transcriptional factor Ying Yang 1 (YY1).
Women with the homozygous TT genotype of rs1271572 had a significantly higher risk in developing breast cancer. Breast cancer patients with the TT genotype of rs1271572 had lower five-year survival rates than those with other genotypes and were more likely to suffer brain metastases. The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.
TT genotype of rs1271572 is associated with increased risk for breast cancer in Chinese women and is associated with unfavored prognosis in Chinese breast cancer patients. TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene. Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.
对雌激素受体β（ERβ）基因启动子区域内的单核苷酸多态性（SNP）进行特征分析，并分析ERβ SNP与乳腺癌易感性之间的关联。采用等位基因特异性四引物聚合酶链反应（PCR）测定了873例乳腺癌女性、645例纤维腺瘤女性和700例健康女性中ERβ基因启动子区域5个SNP（rs3020449、rs3020450、rs2987983、rs1271572和rs1887994）的基因型频率。进行Kaplan-Meier生存分析以评估所选rs1271572与乳腺癌预后的关联。进行电泳迁移率变动分析以探究含SNP rs1271572的探针与转录因子阴阳1（YY1）的结合情况。
rs1271572纯合TT基因型的女性患乳腺癌的风险显著更高。rs1271572 TT基因型的乳腺癌患者的五年生存率低于其他基因型患者，且更易发生脑转移。rs1271572 G→T SNP消除了YY1的结合，并在体外降低了ERβ基因启动子0 N的转录活性。
rs1271572的TT基因型与中国女性患乳腺癌风险增加相关，且与中国乳腺癌患者的不良预后相关。rs1271572的TT基因型通过下调ERβ基因启动子0 N的转录活性抑制ERβ基因的表达。我们的数据显示，rs1271572的TT基因型导致YY1结合位点缺失，并降低了ERβ基因启动子0 N的转录活性。
