Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and Lung Cancer: an Updated Meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotidesneeded for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lungcancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial orinconclusive results.
Methods: To better assess the purported relationship, we performed a meta-analysis of 14publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and GoogleScholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association.
Results: Overall, no significant association was detected between the MTHFR C677T polymorphism and LCrisk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increasednon-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TTvs. CC: OR = 1.24, 95%CI = 1.09-1.41; TC vs. CC: OR = 1.11, 95%CI = 1.03-1.20 and TT+TC vs. CC: OR =1.09, 95%CI = 1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreasedLC risk compared with CC genotype carriers.
Conclusions: Our study provided evidence that the MTHFR 677Tnull genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studieswith large sample sizes are warranted to further evaluate this association in more detail.