ERα基因单核苷酸多态性与乳腺癌内分泌治疗药物引发子宫内膜病变相关性

Correlation Between Single Nucleotide Polymorphism of ERαGene and Endometrial Lesions Induced by Endocrine Therapy of Breast Cancer

目的探讨乳腺癌手术后患者应用选择性雌激素受体调节药(SERMs)引起的子宫内膜病变与雌激素受体α(ERα)基因rs9340799、rs2234693位点单核苷酸多态性(SNPs)之间的相关性。方法接受他莫昔芬或枸橼酸托瑞米芬内分泌治疗(>1年)的乳腺癌患者164例,对其血液标本行ERα基因rs9340799、rs2234693位点测序,比较各基因亚型与子宫内膜厚度、阴道诊刮比例之间相关性。结果ERα基因rs9340799位点A/G基因型比A/A及G/G基因型患者子宫内膜更厚、阴道诊刮患者更多(P<0.05)。在同一基因型患者中,不同药物组间(他莫昔芬或枸橼酸托瑞米芬)子宫内膜厚度和诊刮次数差异无统计学意义(P>0.05)。首次子宫内膜诊刮时间与rs9340799位点SNPs存在显著相关性(P<0.01)。同一基因型患者间比较,A/G基因型患者1年内内膜诊刮次数明显多于1年以上者(P<0.05)。结论SERMs相关子宫内膜病变的发生可能与ERα基因表型有关。ERα基因rs9340799与rs2234693位点中,A/G基因型可能是发生子宫内膜病变的易感型基因,携带易感基因的患者在服用药物1年内出现子宫内膜病变比例较高。

Objective To explore the correlation between endometrial lesions induced by selective estrogen receptor modulators(SERMs)and ERαgene rs9340799 and rs2234693 single nucleotide polymorphisms(SNPs)after breast cancer surgery.Methods One hundred and sixty-four breast cancer patients who underwent tamoxifen or toremifene treatment(>1 years)were enrolled and hospitalized.The ERαgene rs9340799 and rs2234693 sites were sequenced and compared the correlation between comparative genotype and endometrial thickness,endometrial scraping rate.Results The ERαgene rs9340799 locus A/G genotype was thicker than the A/A and G/G genotypes,and the number of patients with vaginal curettage was more than(P<0.05).Among the patients with the same genotype,there was no significant difference in endometrial thickness and number of diagnosis between different drug groups(tamoxifen or toremifene citrate)(P>0.05).In addition,a significant correlation was found between the first endometrial scraping time and the rs9340799 SNPs(P<0.01).Compared with patients with the same genotype,the number of endometrial scraping in one year of patients with A/G genotype was significantly more than who were treated more than one year(P<0.05).Conclusion SERMs-related endometrial lesions may be related to ERαgene phenotype.In ERαgene rs9340799 and rs2234693 loci,A/G alleles may be susceptible genes for aromatase inhibitor-related endometrial lesions.Patients with susceptibility genes have a higher rate of endometrial lesions within 1 year of taking the drug.