CYP3A5、GSTP1基因多态性与转移性结直肠癌患者化疗疗效的关系  

Genetic polymorphisms of CYP3A5 and Glutathione S-Stransferase P1 predict clinical outcomes of chemotherapy in metastatic colorectal cancer

作　　者：董宁宁[1] 罗晓雅[1] 何振[1] 

机构地区：[1]首都医科大学附属北京友谊医院消化内科,北京100050

出　　处：《临床和实验医学杂志》2014年第8期607-610,共4页Journal of Clinical and Experimental Medicine

摘　　要：目的探讨细胞色素P450 3A5(CYP3A5)和谷胱甘肽S-转移酶P1(GSTP1)基因多态性与转移性结直肠癌患者化疗疗效及预后的关系。方法收集转移性结直肠癌病人,采用氟尿嘧啶/亚叶酸钙/伊立替康(FOLFIRI)方案化疗,患者每4周期进行疗效评估,并随访记录疾病进展时间。采用基质辅助激光解吸电离飞行时间确定基因型,用χ2检验分析CYP3A5、GSTP1基因型对客观有效率的影响,Kaplan-Meier法进行生存分析,Log-rank检验分析不同基因型患者疾病进展时间差异。结果 63例转移性结直肠癌患者中,携带CYP3A5 GG基因型患者化疗客观有效率(完全缓解+部分缓解)显著高于携带AG/AA基因型患者(57.1%vs.32.1%,P=0.048),Kaplan-Meier生存分析显示携带CYP3A5 GG基因型患者疾病进展时间显著长于AG/AA基因型患者(P=0.012)。GSTP1基因多态性与化疗客观有效率、疾病进展时间无关。结论 CYP3A5基因型与转移性结直肠患者化疗疗效及预后密切相关,为结直肠癌的个体化治疗提供了参考。Objective To investigate the predictive and prognostic value of genetic polymorphisms of cytochrome P450 3A5 （CYP3A5） and glutathione S - stransferase P1 （ GSTP1 ） for patients with metastatic colorectal cancer receiving first - line FOLFIRI chemotherapy. Methods Objective response was evaluated every 4 cycles and progression -free survival time （PFS） was recorded. Genotypes of CYP3A5 and GSTP1 were determined by matrix - assisted laser dasorption/ionization time - of - flight. Х^2 test was used for statistical analysis between CYP3A5 genotype and chemotherapeutic response, and Log - rank test on PFS. Results Among 63 enrolled patients, people with CYP3A5 rs776746 GG geno- type showed both a statistically higher objective response than those with AG/GG genotype （57.1% vs. 32.1%, P = 0. 048 ）, and statistically longer PFS （ P = 0. 012）. Whereas, no statistical difference was found between GSTP1 polymorphisms and objective response or PFS. Conclu- sion CYP3A5 rs776746 A 〉 G polymorphisms have a predictive and prognostic contribution towards FOLFIRI regimen in metastatic colorectal cancer. This could represent a further step towards personalized therapy.

关 键 词：转移性结直肠癌 药物代谢酶 基因多态性 化学治疗 

分 类 号：R735.34[医药卫生—肿瘤]