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.
Department of Respiratory Medicine, the Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin, China. houxinheng@hotmail.com
Xin-Heng
XH
Hou
Yu-Min
YM
Huang
Yuan-Yuan
YY
Mi
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)