Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma

Published studies on the relationships between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and lung cancer risk. A total of 15 studies including 10,753 cases and 11,275 controls described C677T genotypes, among which 11 articles totalling 6,161 cases and 7,684 controls described A1298C genotypes, were also involved in this meta-analysis. Overall, no significantly elevated lung cancer risk was found in any genetic models when all studies were pooled. For C677T polymorphism: (TT vs. CC: OR = 1.17, 95% CI = 0.97-1.42; TC vs. CC: OR = 1.06, 95% CI = 0.94-1.20; dominant model: OR = 1.09, 95% CI = 0.96-1.24; and recessive model: OR = 1.08, 95% CI = 0.95-1.24); for A1298C polymorphism: (CC vs. AA: OR = 1.04, 95% CI = 0.91-1.19; AC vs. AA: OR = 0.98, 95% CI = 0.91-1.06; dominant model: OR = 0.99, 95% CI = 0.92-1.06; and recessive model: OR = 1.05, 95% CI = 0.92-1.20). In the subgroup analyses, the results showed that 677T varients could decrease lung cancer risk in female (OR = 0.63, 95% CI = 0.41-0.95, P-value = 0.03, 677CC as reference). No evidence of any associations of MTHFR A1298C polymorphism with lung cancer was found in overall or subgroup analyses. Our meta-analysis supports that the common polymorphisms of C677T and A1298C in MTHFR gene are not susceptibility gene for lung cancer from currently available evidence.