Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC + AC vs. AA), and recessive model (CC vs. AC + AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR = 0.99, 95% CI 0.94-1.05; CC vs. AA: OR 0.99, 95% CI 0.90-1.09; dominant model: OR = 0.99, 95% CI 0.95-1.04; and recessive model: OR = 0.98, 95% CI 0.90-1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.