MTHFR C677T基因多态性与晚期非小细胞肺癌化疗不良反应的关系

摘要

背景与目的：亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase，MTHFR)是叶酸代谢的关键酶，在DNA甲基化中起重要作用。本研究旨在探讨MTHFR C677T多态性与晚期非小细胞肺癌(non-small cell lung cancer，NSCLC)化疗不良反应的关系。方法：收集2007年6月-2009年5月在浙江省肿瘤医院经病理学确诊的晚期NSCLC患者100例。所有患者均接受铂类药物联合吉西他滨的方案化疗。用等位基因特异-PCR技术检测患者MTHFR基因型。结果：100例晚期NSCLC患者中，MTHFR C677T T/T、T/C和C/C基因型频率分别为20%、44%和36%。在血液学不良反应中，C/C基因型血小板减少发生率较T/T、T/C基因型低，差异有统计学意义(P=0.039)。本研究未发现MTHFR各基因型与化疗后恶心、呕吐不良反应相关。结论：MTHFR C677T基因多态性对预测晚期NSCLC含铂类药物方案化疗后不良反应有临床意义。%Background and purpose:Methylene tetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. This study aimed to investigate the relationship between methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and chemotherapy side effects in advanced non-small cell lung cancer (NSCLC) patients. Methods:A total of 100 patients with advanced NSCLC conifrmed by pathology were included into this study in Zhejiang Cancer Hospital from Jun. 2007 to May. 2009. All patients received the combined chemotherapy of platinum drug and gemcitabine. MTHFR genotypes were determined by allele-specific-PCR technology. Results:In the 100 cases, genotype frequency of MTHFR C677T T/T, T/C and C/C were 20%, 44%and 36%, respectively. Compared with patients of T/T and T/C genotype, patients of C/C genotype were correlated with decreased rate of thrombocytopenia to chemotherapy (P=0.039). No signiifcant differences were observed concerning gastrointestinal toxicity. Conclusion:MTHFR C677T gene polymorphism can be used to predict the adverse reactions to platinum-based chemotherapy in patients with advanced NSCLC.