ESR1基因单核苷酸多态性与乳腺癌内分泌治疗疗效的关系

目的了解雌激素受体基因(ESR1)单核苷酸多态性(SNP)位点在乳腺癌患者中的分布及其基因型与内分泌治疗疗效的关系。方法选取ESR1基因15个SNP位点(rs872921、rs2077647、rs3904766、rs2234693、rs11155816、rs827419、rs2347867、rs3798759、rs 1801132、rs985191、rs9340931、rs9397463、rs722209、rs3778099和rs3798577)作为遗传标记,运用PCR-限制性片段长度多态性分析、PCR-测序分析和荧光定量等位基因特异性PCR的方法对240例接受内分泌治疗的乳腺癌患者进行SNP基因分型。结果rs872921、rs3904766位点因多态性低被舍弃,其余位点存在多态性。rs2077647、rs3798759位点的等位基因型及基因型与内分泌治疗疗效相关,差异有统计学意义(P<0.05)。连锁不平衡(LD)分析和单倍型分析显示在ESR1基因上存在4个LD区,rs2077647~rs2234693(LD1)、rs2234693~rs11155816(LD2)、rs9397463~rs722209(LD3)和rs3778099~rs3798577(LD4),其中LD2和LD3组成的单倍型与内分泌治疗疗效相关(P<0.05)。rs11155816~rs827419、rs2347867~rs1801132组成的单倍型亦与内分泌治疗疗效相关(P<0.05)。结论ESR1基因上部分SNP位点及其形成的单倍型与内分泌治疗疗效相关,可能用于预测乳腺癌对内分泌治疗的反应。

Relationship between single nucleotide polymorphism of ESR1 gene and endocrine therapy efficacy in breast cancer

Objective To explore the distribution of single nucleotide polymorphism(SNP) loci of estrogen receptor(ESR1) gene in breast cancer patients and to study the relationship between the SNP genotypes and the efficacy to endocrine therapy. Methods Fifteen SNP loci(rs872921,rs2077647,rs3904766,rs2234693,rs11155816,rs827419,rs2347867,rs3798759,rs 1801132,rs985191,rs9340931,rs9397463,rs722209,rs3778099 and rs3798577) of ESR1 gene were selected as genetic markers.PCR-restriction fragment length polymorphisms,PCR-DNA sequencing and allele-specific real time PCR methods were employed to analyze the loci genotype of 240 patients with breast cancer accepted endocrine therapy. Results The loci rs872921 and rs3904766 were abandoned for poor ploymorphisms,and the other 13 loci had polymorphisms.The frequencies of alleles and genotypes of rs2077647 and rs3798759 were significantly related with the efficacy of endocrine therapy(P<0.05).The linkage disequilibrium and the hapotype analysis showed that there were four linkage disequilibrium blocks in ESR1 gene.They were rs2077647-rs2234693(LD1),rs2234693-rs11155816(LD2),rs9397463-rs722209(LD3) and rs3778099-rs3798577(LD4)and the hapotypes of LD2,LD3,s11155816-rs827419 and rs2347867-rs1801132 were positively related with the efficacy of endocrine therapy(P<0.05).Conclusion Some of the polymorphisms of ESR1 gene and the haplotypes are positively associated with the endocrine therapy efficacy,and maybe account for predicting the endocrine response in breast cancer.