Cumulative review and meta-analyses on the association between MTHFR rs1801133 polymorphism and breast cancer risk: a pooled analysis of 83 studies with 74,019 participants.

Background: The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To clarify the precise effects of MTHFR polymorphisms on the risk of breast cancer, a systemic review and most comprehensive meta-analysis of all available studies relating MTHFR rs1801133 gene polymorphism to the risk of breast cancer was conducted.

Methods: Eligible articles were identified by search of databases including Medline (Mainly PubMed), Embase, Web of Science, Chinese Biomedical Literature database (CBM), CNKI and Wanfang Medical databases. Crude ORs with 95% CIs were used to assess the strength of association.

Results: Finally, a total of 83 studies with 35,029 cases and 38,990 controls were included. Overall, MTHFR rs1801133 gene polymorphism was proved to contribute to the risk of breast cancer under all genetic models (TT vs. CC: Pheterogeneity <0.001, OR=1.141, 95%CI=1.065-1.222, P <0.001; TT vs. CT: Pheterogeneity <0.001, OR=1.085, 95%CI=1.021-1.154, P=0.009; TT + CT vs. CC: Pheterogeneity <0.001, OR=1.040, 95%CI=1.020-1.061, P <0.001; TT vs. CC + CT: Pheterogeneity <0.001, OR=1.131, 95%CI=1.052-1.215, P=0.0478; T allele vs. C allele: Pheterogeneity <0.001, OR=1.040, 95%CI=1.009-1.071, P=0.010).

Conclusions: The results of this meta-analysis suggest that MTHFR rs1801133 gene polymorphism may the therapeutic target for breast cancer.