亚甲基四氢叶酸还原酶基因C677T多态性与肺腺癌化疗疗效的关系

Correlation of methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism and chemotherapy efficacy in lung adenocarcinoma

目的观察肺腺癌患者亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与化疗疗效的关系。方法化疗前抽取92例肺腺癌患者外周血液,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多态性,并分析其与化疗的疗效关系。结果 92例肺腺癌患者中,MTHFR基因C677T野生型(CC)的分布为60.9%(56/92),纯合突变型(TT)为14.1%(13/92),杂合突变型(CT)为25.0%(23/92)。一线化疗方案使用培美曲塞/卡铂的疗效:野生型(CC)PR 20例,SD 19例,PD 17例,总有效率(ORR)为35.7%;纯合突变型(TT)PR 2例,SD 7例,PD 4例,ORR为15.4%;杂合突变型(CT)SD 13例,PD 10例,ORR为0。CC型患者化疗ORR显著高于TT型和CT型者(P=0.001)。CC型与TT型/CT型患者的肿瘤进展时间(TTP)分别为6.2个月和4.7个月,差异有统计学意义(P=0.023)。二线化疗方案使用吉西他滨/奈达铂或多西紫杉醇/奈达铂的疗效:CC型PR 2例,SD 5例,PD 10例;TT型SD 3例;CT型PR 1例,SD 2例,PD 7例,CC型与TT型/CT型患者的ORR比较,差异无统计学意义(P=1.000)。结论 MTHFR基因C677T野生型(CC)肺腺癌患者可能是使用培美曲塞联合卡铂化疗有效的人群。MTHFR基因C677T CC型患者的TTP显著长于TT型患者和CT型患者。MTHFR基因C677T多态性与吉西他滨/奈达铂或多西紫杉醇/奈达铂化疗疗效无关。

Objective To investigate a possible correlation between C677T polymorphism in the methylenetetrahydrofolate reductase （MTHFR） gene and chemotherapy efficacy in patients with pulmonary adenocarcinoma. Methods Peripheral blood samples from 92 patients with pulmonary adenocarcinoma were collected before chemotherapy,and the C677T polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）.We examined whether genotype correlated with whether the patients showed partial response（PR）, stable disease（SD） or progressive disease（PD） following chemotherapy. Results Of the 92 patients,56 （60.9%） had wild-type genotype （CC）,13（14.1%） were homozygous mutant（TT）,and 23（25.0%） were heterozygous mutant （CT）.Among the patients treated with pemetrexed/carpoplatin as first-line regimen,CC patients showed an overall response rate（ORR）of 35.7%, with 20 CC patients achieving PR;19,SD;and 17,PD.Among TT patients,ORR was 15.4%,with 2 patients achieving PR;7,SD; and 4,PD.Among CT patients,ORR was 0,with 13 achieving SD and 10,PD.ORR was significantly higher in CC patients than in TT or CT patients（P=0.001）.In addition,CC patients showed significantly longer time to progression（6.2 months） than did TT or CT patients（4.7 months;P=0.023）.Among the patients treated with gemcitabine/nedaplatin or docetaxel/nedaplatin as second-line regimen,2 CC patients showed PR;5,SD;and 10,PD.3 TT patients achieved SD;among CT patients, 1 achieved PR,2 SD and 7,PD.ORR was similar between CC and TT/CT patients（P=1.000）. Conclusions Pemetrexed in combination with carboplatin may be associated with greater therapeutic efficacy and longer time to progression in CC patients than in TT/CT patients.However, genotype at the MTHFR C677T polymorphism does not appear to influence the therapeutic efficacy of gemcitabine/nedaplatin or docetaxel/nedaplatin.