Correlation Between Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphisms and Pemetrexed Chemotherapy Efficacy/Toxicity in Non-Squamous Non-Small Cell Lung Cancer

BACKGROUND: In the present study, we aimed to retrospectively analyze the correlation between toxicity of pemetrexed (PEM) chemotherapy and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). MATERIAL/METHODS: We used polymerase chain reaction, gene scanning, and restriction fragment length polymorphism to analyze MTHFR C677T in 51 patients with advanced non-sq NSCLC. The patients received chemotherapies with single-agent PEM (monotherapy group) or with PEM combined with cisplatin (joint group). The correlation between MTHFR C677T polymorphisms and chemotherapy efficacy/toxicity was also assessed. RESULTS: There were 40 patients in the monotherapy group and 11 patients in the joint group. Among the 40 patients received single-agent PEM chemotherapy, those with the CT/TT genotype had higher incidence of leukopenia, neutropenia, nausea, and fatigue compared to patients with the with wild-type genotype CC (all P<0.05). However, polymorphisms of MTHFR C677T were not significantly associated with other adverse events and clinical outcomes. CONCLUSIONS: Compared with genotype CC (the wild type), patients with the CT/TT genotype had higher incidence of leukopenia, neutropenia, nausea, and fatigue. Therefore, the MTHFR C677T polymorphism could be a predictive factor for leukopenia, neutropenia, nausea, and fatigue toxicities in non-sq NSCLC patients treated with single-agent PEM.