MTHFR,GSTP1,ERCC1基因多态性与结直肠癌FOLFOX化疗方案疗效相关性研究

Association of MTHFR,GSTP1,ERCC1 polymorphisms and response to FOLFOX in colorectal cancer patients

目的:探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR),谷胱甘肽S转移酶P1(glutathione S-transferase pi-1,GSTP1),核苷酸切除修复交叉互补组-1(excision repair cross-complementing group 1,ERCC1)基因多态性与结直肠癌5-氟尿嘧啶/奥沙利铂/亚叶酸钙(FOLFOX)化疗方案疗效的相关性。方法:150例晚期大肠癌患者抽取静脉血并提取DNA,用荧光定量PCR和高分辨率溶解曲线分型技术(HRM-SNP)等方法检测患者MTHFR、GSTP1、ERCC1基因型。所有患者均经FOLFOX方案治疗,以实体瘤化疗疗效评价标准(RECIST1.1)评价疗效。运用SPSS 19.0结合临床资料进行统计分析。结果:⑴患者性别,年龄,结直肠癌分期(TNM),肿块部位等和FOLFOX化疗疗效均无明显相关性(P>0.05)。⑵GSTP1Ile105Val Ile/Ile和Ile/Val+Val/Val有效率分别为19.7%、20.5%,两组基因型之间的OR值为2.876,95%CI(1.288,6.424),P<0.05;MTHFR Ala222 Val Ala/Ala和Ala/Val+Val/Val有效率分别为11.8%、28.3%,OR值为2.236,95%CI(1.020,5.017),P<0.05。结论:GSTP1Ile105Val、MTHFR Ala222Val单核苷酸多态性与结直肠癌对FOLFOX方案化疗疗效相关,检测GSTP1 Ile105Val、MTHFR Ala222Val单核苷酸多态性可能成为预测结直肠癌患者接受FOLFOX方案化疗疗效的指标。

AIM： To investigate the relation- ship between the polymorphisms of MTHFR, GSTP1, ERCC1 and the response to FOLFOX chemotherapy in advanced colorectal cancer. METHODS. A total of 150 patients diagnosed as an advanced colorectal cancer by the pathology were treated with FOLFOX chemotherapy and DNA of peripheral blood-leukocytes was ob-tained before the treatment, MTHFR, GSTP1, ERCC1 genetype were detected by the HRM- SNP method. RESULTS： （1） The frequencies of MTHFR429 Glu/Glu, Glu/Ala, Ala/Ala were 59.1%, 37.0%, 3.9%; MTHFR 222 Ala/Ala, Ala/Val, Val/Val were 12.6% ,47.2% ,40.% GSTPI-105 Ile/Ile, Ile/Val,Val/Val genetypes were 63.0%, 33.1%, 3.9%; ERCCl-118AA, AT,TT genetypes were 50.4%, 41.7% ,7.9% , respectively. （2）The effective rate of FOLFOX chemotherapy among patients with GSTPI-105 Ile/Ile, Ile/Val ＋ Val/Val genetypes were 19.7% , 20.5% , OR = 2. 876, 95% CI （1. 288, 6. 424）,P〈0.05;MTHFR 222 Ala/Ala, Ala/ Val＋Val/Val genetypes were 11.8% , 28.3%, OR=2. 236, 95% CI （1. 020,5. 017）, P〈0.05, respectively,which was a significant difference. CONCLUSION. The polymorphisms of MTH-FR,GSTP1, ERCC1 correlates with the clinical response to FOLFOX chemotherapy and the genetype detected by the HRM-SNP method may be a predictor of sensitivity to FOLFOX chemotherapy.