乳腺癌分子分型与GSTM1、GSTT1和GSTP1(rs1695)基因多态性的关系及意义

The correlationship and its clinical significance between gene polymorphisms of GSTM1, GSTT1 and GSTP1 with molecular classification in breast cancer

目的探讨乳腺癌患者谷胱甘肽转硫酶M1(GSTM1)、谷胱甘肽转硫酶T1(GSTT1)和谷胱甘肽转硫酶P1(GSTP1 rs1695)的基因多态性分布,并分析其与乳腺癌分子分型的关系。方法应用多重PCR技术(MPCR)和高分辨融解曲线技术(HRM)分析252例女性乳腺癌患者外周血中GSTM1、GSTT1和GSTP1(rs 1 695)的基因多态性。结果 252例乳腺癌患者中,108例(42.9%)为GSTM1(+),144例(57.1%)为GSTM1(-);178例(70.6%)为GSTT1(+),74例(29.4%)为GSTT1(-);143例(56.7%)为GSTP1(rs1695)AA基因型,102例(40.5%)为GSTP1(rs1695)AG基因型,7例(2.8%)为GSTP1(rs1695)GG基因型。经Hardy-Weinberg遗传平衡检验,证实本研究入组病例GSTP1(rs1695)基因具有群体代表性(P>0.05);8例Cerb-B-2(2+)和(2+→3+)者未行FJSH检测予以剔除,其中Luminal型占63.1%(154/244),三阴型占22.1%(54/244),Her-2过表达型占14.8%(36/244);GSTT1(-)在不同分子分型的乳腺癌人群中的分布不同,差异有统计学意义(P<0.05),而GSTM1和GSTP1(rs1695)基因多态性在各分子分型的乳腺癌人群中的分布差异无统计学意义(P>0.05)。结论 GSTT1基因多态性与乳腺癌的分子分型有关,GSTT1(-)在三阴型乳腺癌中缺失率较低,其基因多态性可为分子分型下乳腺癌的异质性提供合理补充。

Objective To investigate the distribution of GSTM1, GSTI＇I and GSTP1 （rs1695） gene polymorphisms inpatients with breast cancer,and to analysis the relationship between three genes polymorphsms with molecular classification of breast cancer. Methods The gene polymorphisms of GSTM1 ,GSTI＇I and GSTP1 （rs1695） were analyzed using multiply PCR technique and High Resolution Melting in 252 female breast cancers. Results In 252 cases of breast cancer,GSTM1 （ ＋ ） genotype accounting for 42.9% （108/252） ,GSTM1 （ - ） genotype accounting for 57.1% （144/252） ;GSTrl （ ＋ ） genotype accounting for 70.6% （178/252） ,GSTT1 （ - ） genotype accounting for 29.4% （74/ 252） ;GSTP1 （rs1695） AA genotype accounting for 56.7% （143/252）, GSTP1 （ rs1695 ） AG genotype accounting for 40.5% （ 102/252 ）, GSTP1 （rs1695） GG genotype accounting for 2.8% （7/252）,GSTP1 （rs1695） enrolled into our research had a group representation （P 〉 0.05） suggested by the hardy - Weinberg test. 8 cases of Cerb - B - 2 expression （2 ＋ ） and （2 ＋ to 3 ＋ ） were excluded because they were not verified by FJSH test,the Luminal subtype accounting for 63.1% （154/244） ,Triple negative subtype accounting for 22. 1% （54/244） ,Her -2 subtype accounting forl4.8% （36/244） ;there was statistic difference between GSTY1 polymorphism with molecular classification in breast cancers （P 〈0. 05 ）,while there were no statistic difference between GSTM1, GSTP1 （rs1695） polymorphism with molecular classification in breast cancers （P 〉 0.05）. Conclusion There was statistic difference between GSTI＇I polymorphism with molecular classification in breast cancer,the GSTrl （ - ） rate accounting lower in Triple negative subtype. GSTrl polymorphism might provide reasonable supplement to Hetero- geneity of breast cancer.