Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to lung cancer as well as response to chemotherapy: a meta-analysis based on 31 studies

Background: Conflicting results have been reported regarding the correlation of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of lung cancer as well as response to chemotherapy. Objective: To estimate the correlations of the MTHFR C677T polymorphism and risk of lung cancer as well as response to chemotherapy by conducting a meta-analysis. Methods: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, CKNI, VIP, and Wanfang database through January 2015. Only casecontrol studies evaluating the MTHFR C677T polymorphism and lung cancer risk or response to chemotherapy were eligible. Results: Thirty-one case-control studies involving 12,878 cases of lung cancer and 12,447 controls were analyzed. The MTHFR C677T gene polymorphism was associated with lung cancer susceptibility in three genetic models (TT vs. CT+CC: odds ratio [OR] = 1.250, 95% confidence interval [CI] 1.076-1.452; TT vs. CC: OR = 1.324, 95% CI 1.095-1.601; and T vs. C: OR = 1.126, 95% CI 1.024-1.239). Stratified analyses indicated significantly increased lung cancer risks were consistently indicated in Asian patients and for non-small cell lung cancer (NSCLC) but not in European patients or for small cell lung cancer. Patients carrying the TT+CT genotype had a 47.9% lower response rate (OR = 0.521, 95% CI 0.361-0.753) to chemotherapy than the CC allele carriers. However, the differences were not significant for the other genetic models. Conclusions: The MTHFR C677T polymorphism is associated with an increased risk of lung cancer in Asian patients and with the NSCLC subtype. Moreover, the MTHFR 677T mutation might lower the response to chemotherapy.