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

Abstract

BackgroundIn 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/MethodsWe 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.ResultsThere 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.ConclusionsCompared 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.

The Role of Single-Nucleotide Polymorphisms in Cholangiocarcinoma: A Systematic Review

“…The underlying mechanism may be related to response to therapy in these cases. MTHFR rs1801131 interacts with the metabolism of fluoropyrimidines and platinum drugs and is known to affect the efficiency of chemotherapy in colorectal, breast and non-small-cell lung cancers [ 144 , 145 , 146 ]. As 5-fluorouracil and cisplatin are also used in systemic therapy for CCA, this might explain the prognostic effect of MTHFR rs1801131 [ 147 , 148 ].…”