以培美曲塞为基础治疗晚期非小细胞肺癌疗效与亚甲基四氢叶酸还原酶C677T基因多态性相关性的Meta分析

Association between MTHFR C677T polymorphism and the efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer:a Meta-analysis

目的探讨以培美曲塞为基础治疗晚期非小细胞肺癌疗效与亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性的相关性。方法计算机检索PubMed、Embase、Cochrane Library、中国知网、万方、维普数据库,筛选关于培美曲塞为基础治疗晚期非小细胞肺癌疗效与MTHFR C677T基因多态性相关性的队列研究。使用RevMan 5.3和Stata 15.0软件,分别以显性、隐性基因模型对基因多态性与化疗疗效的相关性进行Meta分析。结果共纳入9项研究,均为队列研究。Meta分析结果显示:显性遗传模型中(CC vs.CT+TT),CC基因型患者较CT+TT基因型患者,以培美曲塞为基础化疗,客观有效率(ORR)显著提高,相对危险度(RR)值为2.93(95%CI:1.80~4.76,P<0.001),差异有统计学意义;而疾病控制率和远期疗效差异无统计学意义。隐性遗传模型中(TT vs.CT+CC),TT基因型患者与CT+CC基因型患者相比,以培美曲塞为基础化疗,近远期疗效差异均无统计学意义。结论MTHFR C677T基因CC型的晚期非小细胞肺癌患者采用培美曲塞为基础化疗的客观缓解率较其他基因型更高,但因纳入研究的数量及质量有限,仍需更多高质量、大样本的前瞻性研究加以验证。

Objective To evaluate the relationship between methylenetetrahydrofolate reductase(MTHFR)C677 T polymorphism and pemetrexed-based chemotherapy in patients with advanced non-small cell lung cancer.Methods The PubMed,Embase,Cochrane Library,CNKI,Wanfang,and VIP databases was searched to select the cohort studies about the association between MTHFR C677 T gene polymorphism and pemetrexed-based chemotherapy in patients with advanced nonsmall cell lung cancer.The RevMan 5.3 and Stata 15.0 software was used for statistical analysis.Results A total of 9 cohort articles were enrolled in.In the dominant genetic model(CC vs.CT+TT),the objective response rate(ORR)of pemetrexed based chemotherapy in patients with CC genotype was significantly higher than CT+TT genotype,and the relative risk(RR)value was 2.93(95%CI:1.80-4.76,P<0.001).There was no significant difference in disease control rate and long-term efficacy.In the recessive genetic model(TT vs.CT+CC),There was no significant difference in the short-term and long-term efficacy of pemetrexed based chemotherapy between patients with TT gene and CT+CC gene.Conclusion Patients with MTHFR C677 C genotype of advanced non-small cell lung cancer who receiving pemetrexed combined chemotherapy have a higher objective response rate than other genotypes.More prospective studies with higher quality and larger samples are needed to be validated due to the limited number and quality of the included studies.