Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Objective:The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase(MTHFR) C677T excision repair cross-complementation group 1(ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer(NSCLC).Methods:A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens.The polymorphisms of MTHFR C677T,ERCC1 C8092A,and ERCC1 C118T were genotyped using the TaqMan methods.Results:The overall response rate was 28.9%.Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype(TT or CT)(41.2% versus 19.1%,P=0.01).Median time to progression(TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype(7.6 months versus 5.0 months,P=0.003).No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival.Conclusions:Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.