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ERα基因SNPs与乳腺癌芳香化酶抑制剂治疗所致骨代谢异常的关系 被引量:10

Genetic polymorphism of ERα gene is associated with bone loss in women taking aromatase inhibitor for breast cancer
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摘要 目的探讨接受芳香化酶抑制剂(AIs)治疗的乳腺癌患者ERα基因rs9340799、rs2234693位点单核苷酸多态性(SNPs)与AIs所致骨代谢异常的相关性。方法随机选取160名接受AIs治疗的乳腺癌术后患者,排除影响骨代谢的疾病,提取全基因组DNA并进行PCR扩增,对rs9340799、rs2234693位点进行单向测序;用双能X线吸收法测定腰椎(L1-4)骨密度(BMD)。结果 ERα基因rs9340799位点各基因型受试者的腰椎BMD存在显著性差异(P<0.01),A/A型高于A/G型及G/G型(P<0.01);rs2234693位点各基因型间的腰椎BMD亦存在显著性差异(P<0.01),T/T型、C/T型均高于C/C型(P<0.01)。去除绝经年数的影响,两位点各基因型受试者间腰椎BMD的差异仍具有统计学意义(P<0.01)。根据接受AIs治疗时间分层分析,两位点SNPs与服药1年内受试者的腰椎BMD相关(P<0.01),在服药1年及以上的受试者中,rs9340799位点SNP与腰椎BMD相关(P<0.05)。结论 ERα基因rs9340799、rs2234693位点SNPs与接受AIs治疗的乳腺癌患者的腰椎BMD存在显著性关联。与纯合基因型A/A型、T/T型相比,杂合基因型A/G型、C/T型及纯合基因型G/G型、C/C型更具有发生骨代谢异常的可能。 Objective The objective of this study is to determine the influence of the polymorphisms of the ERα gene on bone loss among patients taking Aromatase inhibitors( AIs) for estrogen receptor positive( ER +) breast cancer. Methods The subjects consisted of 160 postmenopausal women with ER + breast cancer who were taking third-generation AIs. Those who had conditions which affect bone metabolism were excluded. Whole genome was extracted from each participant's peripheral blood and target region was amplified and sequenced. Bone mineral density( BMD) was measured by dual energy x-ray absorptiometry. Results Women with G / G genotype for the rs9340799 or with C / C genotype for the rs2234693 showed significantly greater bone loss at the spine relative to patients carrying the A allele( A / A,A / G) or T allele( T / T,T / C),both P〈0. 01. Eliminated the influence of postmenopausal years and the length of taking AIs,the results were mostly similar. Conclusion Patients with the A / G and G / G genotype for the rs9340799 or C / T and C / C genotype for the rs2234693 polymorphism in the ERα gene are at risk for AI-associated bone loss and deserve close follow-up during long-term AIs therapy.
出处 《中国骨质疏松杂志》 CAS CSCD 北大核心 2016年第8期998-1003,共6页 Chinese Journal of Osteoporosis
基金 上海市中医药事业发展三年行动计划资助(ZY3-CCCX-2-1002)
关键词 ERα基因 单核苷酸多态性 乳腺肿瘤 芳香化酶抑制剂 骨质疏松 骨密度 骨代谢 ERα Polymorphisms Breast cancer Aromatase inhibitors Osteoporosis Bone mineral density Bone metabolism
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参考文献18

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二级参考文献32

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