GSTP1、GSTM1基因多态性与顺铂导致骨髓抑制的相关性研究
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摘要
目的考察顺铂致骨髓抑制与谷胱甘肽硫转移酶P1(GSTP1)和谷胱甘肽硫转移酶M1(GSTM1)基因多态性的关系。方法用病例对照研究的方法考察以顺铂为主要化疗方案的100例癌症初治肿瘤化疗患者基因多态性与骨髓移植的相关性,白细胞计数和血小板的数量为指标判断是否发生了骨髓抑制以及骨髓抑制程度。提取DNA扩增测序法判断GSTP1、GSTM1基因型。结果 GSTP1的3种基因型AA、AG、GG型均存在,并且在62例发生骨髓抑制的病例中,GSTP1 AG/GA型的患者的分布明显高于GSTP1 AA型患者。GSTM1包含缺失(-)和非缺失(+)2种基因型,100例病例中GSTM1(+)少于GSTM1(-)。Logistic分析结果表明GSTP1 AG/GG型是顺铂致骨髓抑制的独立危险因素,GSTM基因缺失虽不是顺铂致骨髓抑制的独立危险因素,但能促进GSTP1 AG/GG型的作用,导致顺铂致骨髓抑制进一步加重。结论顺铂导致的骨髓抑制程度与GSTP1基因多态性相关。
Objective To investigate the relationship between bone marrow suppression induced by cisplatin and GSTP1 or GSTM1 gene polymorphism,Methods Case-control study was adopted to investigate 100 newly diagnosed cancer patients undergoing chemotherapy treated with cisplatin as chemotherapy regimen. WBC and PLT were determined as marrow suppression index. GSTP1 and GSTM1 genotypes were determined by PCR method. Results GSTP1 had three genotypes as AA, AG, and GG gentype. Among 62 cases suffering from marrow suppression, distributions of GSTP1 genotype AG/GA were higher significantly than those of GSTP1 AA gentype. GSTM1 included 2 genotypes as deletion(-) and non deletion(+), and cases of GSTM1(+) were less than GSTM1(-). Logistic analysis showed that GSTP1 AG/GG type was an independent risk factor for cisplatin-induced myelosuppression. GSTM gene deletion was not an independent risk factor for cisplatin-induced myelosuppression, but it could promote the effect of GSTP1 AG/GG type, leading to further aggravation of cisplatin-induced myelosuppression. Conclusion Cisplatin induced myelosuppression is associated with GSTP1 gene polymorphism
Objective To investigate the relationship between bone marrow suppression induced by cisplatin and GSTP1 or GSTM1 gene polymorphism,Methods Case-control study was adopted to investigate 100 newly diagnosed cancer patients undergoing chemotherapy treated with cisplatin as chemotherapy regimen. WBC and PLT were determined as marrow suppression index. GSTP1 and GSTM1 genotypes were determined by PCR method. Results GSTP1 had three genotypes as AA, AG, and GG gentype. Among 62 cases suffering from marrow suppression, distributions of GSTP1 genotype AG/GA were higher significantly than those of GSTP1 AA gentype. GSTM1 included 2 genotypes as deletion(-) and non deletion(+), and cases of GSTM1(+) were less than GSTM1(-). Logistic analysis showed that GSTP1 AG/GG type was an independent risk factor for cisplatin-induced myelosuppression. GSTM gene deletion was not an independent risk factor for cisplatin-induced myelosuppression, but it could promote the effect of GSTP1 AG/GG type, leading to further aggravation of cisplatin-induced myelosuppression. Conclusion Cisplatin induced myelosuppression is associated with GSTP1 gene polymorphism
引文
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[5]Long X D,Ma Y,Wei Y P,et al.The polymorphisms of GSTM1,GSTT1,HYL1*2,and XRCC1,and aflatoxin B1-related hepatocellular carcinoma in Guangxi population,China[J].Hepatol Res,2006,36(l):48-55.
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[8]田慎之,张建国,肖琪,等.GSTM1、GSTT1及GSTP1基因多态性与广东地区汉族人群喉癌遗传易感性关系的研究[J].临床耳鼻咽喉头颈外科杂志,2011,25(5):204-210.
[9]祁娅妮.谷胱甘肽硫转移酶基因多态性与非霍奇金淋巴瘤临床特征及化疗关系的初步研究[D].太原:山西医科大学,2012.
[2]Stacy A Q,Andrew F O.GSTM1,GSTT1,and risk of squamous cell carcinoma of the head and neck[J].Am J Epidemiol,2001,154(2):95-105.
[3]陈坤,蒋沁婷,马新源,等.谷脱甘肤转移酶T1和Ml基因多态性及吸烟与结直肠癌关系的对照研究[J].中华肿瘤杂志2004,26(11):645-648.
[4]林东晰,唐永明,陆士新,等.谷胱甘肽转硫酶Ml和T1基因型与食管癌危险性:病例一对照研究[J].中华流行病学杂志,1998,19(4):195-199.
[5]Long X D,Ma Y,Wei Y P,et al.The polymorphisms of GSTM1,GSTT1,HYL1*2,and XRCC1,and aflatoxin B1-related hepatocellular carcinoma in Guangxi population,China[J].Hepatol Res,2006,36(l):48-55.
[6]Schneider J,Bernges U,Philipp M,et al.GSTM1,GSTT1,and GSTP1 polymorphism and lung cancer risk in relation to tobacco smoking[J].Cancer Lett,2004,208(1):65-74.
[7]Yang Q,Shu X O,Ruan Z X,et al.Genetic polymorphisms in glutathione-S-transferase carcinoma[J].Cancer,2005,103(1):B52.
[8]田慎之,张建国,肖琪,等.GSTM1、GSTT1及GSTP1基因多态性与广东地区汉族人群喉癌遗传易感性关系的研究[J].临床耳鼻咽喉头颈外科杂志,2011,25(5):204-210.
[9]祁娅妮.谷胱甘肽硫转移酶基因多态性与非霍奇金淋巴瘤临床特征及化疗关系的初步研究[D].太原:山西医科大学,2012.