亚甲四氢叶酸还原酶基因多态性与培美曲塞联合卡铂治疗肺腺癌疗效的关系  

The relationship between polymorphisms genes C677T and A1298C of methylenetetrahydrofolate reductase and the chemotherapy efficacy of pemetrexed combined with carboplatin in lung adenocarcinoma patients

作　　者：董翠梅[1] 康马飞[1] 赵燕仪[1] 林静[1] 陶利英[1] 

机构地区：[1]桂林医学院附属医院肿瘤内科,广西桂林541001

出　　处：《川北医学院学报》2015年第5期618-621,共4页Journal of North Sichuan Medical College

基　　金：广西卫生厅计划课题(Z2012426)

摘　　要：目的:探讨肺腺癌患者亚甲四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T和A1298C多态性与培美曲塞联合卡铂化疗疗效的关系。方法:选取92例肺腺癌患者,化疗前取患者外周血,使用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法检测MTHFR基因C677T和A1298C多态性。结果:所有患者中,MTHFR基因C677T野生型(CC)、纯合突变型(TT)、杂合突变型(CT)频度分别为60.9%、25.0%和14.1%,其总有效率(ORR)分别为35.7%、15.4%和0.0%,CC型ORR显著高于CT型(P=0.001)。CC型与TT型患者的疾病进展时间(TTP)分别为6.2个月和4.7个月(P=0.023)。MTHFR基因A1298C野生型(CC)、杂合突变型(AC)、纯合突变型(AA)频度分别为15.2%、41.3%和43.5%,ORR分别为21.4%、23.6%和25.0%,TTP分别为(5.3±0.6)个月、(5.1±0.7)个月和(5.2±0.5)个月,A1298C 3种基因分型ORR和TTP比较差异均无统计学意义(P>0.05)。结论:MTHFR基因C677T中CC型患者TTP显著长于TT型/CT型患者,因此CC型患者可能是使用培美曲塞联合卡铂化疗有效的人群。Objective： To investigate the relationship between C677 T and A1298 C polymorphisms in the methylenetetrahydrofolate reductase（ MTHFR） gene and chemotherapy efficacy of pemetrexed combined with carboplatin in patients with lung adenocarcinoma. Methods： A total of 92 patients with lung adenocarcinoma were selected and their peripheral blood samples were obtained before chemotherapy respectively. The polymerase chain reaction-restrictive fragment length polymorphism（ PCR-RFLP） was used to detect the genotype of MTHFR C677 T and A1298 C polymorphisms. Results： The frequencies of MTHFR gene C677 T wild type（ CC）,homozygous mutant（ TT）,heterozygous mutant（ CT） genotypes were 60. 9%,14. 1% and 25. 0%,respectively. The overall response rate（ ORR） was 35. 7%,15. 4% and 0. 0%,respectively. The ORR in patients with CC genotype was significantly higher than that with CT genotype（ P = 0. 001）. The time to progression（ TTP） were 6. 2 months and 4. 7 months in CC type and TT types,respectively（ P = 0. 023）. The frequencies of MTHFR A1298 C gene CC,AC,AA genotypes were 15. 2%,41. 3% and 43. 5%,ORR being21. 4%,23. 6% and 25. 0%,and TTP being（ 5. 3 ± 0. 6） months,（ 5. 1 ± 0. 7） months and（ 5. 2 ± 0. 5） months. There was no statistical significance among each genotype in terms of ORR and TTP（ P〉 0. 05）. Conclusion： The patients with CC genotype were significantly higher than those with genotypes in TTP,and pemetrexed combined with carboplatin may be associated with the better therapeutic efficacy of chemotherapy.

关 键 词：肺腺癌 亚甲四氢叶酸还原酶 基因多态性 化疗 

分 类 号：R734.2[医药卫生—肿瘤]