Methylenetetrahydrofolate reductase gene C677T polymorphism and lung cancer: an updated meta-analysis.

OBJECTIVE

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results.

METHODS

To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar 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 LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR=1.11, 95%CI=1.03-1.19; TT vs. 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% decreased LC risk compared with CC genotype carriers.

CONCLUSIONS

Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail.