The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk in the Chinese population has been widely reported, but results were inconsistent. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified through search of databases including Medline, PubMed, Web of Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI, Chinese), and Wangfang Database (Chinese). The association between the MTHFR polymorphism and breast cancer risk was conducted using odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of 22 studies with 6,103 cases and 7,913 controls were included in our meta-analysis: 13 studies with 3,273 cases and 4,419 controls for C677T polymorphism and 9 studies with 2,830 cases and 3,494 controls for A1298C polymorphism. With regard to C677T polymorphism, significant association was found with breast cancer risk under three models (T vs. C: OR = 1.12, 95 % CI = 1.02-1.23, P = 0.015; TT vs. CC: OR = 1.35, 95 % CI = 1.10-1.67, P = 0.005; TT vs.
Cc/ct: OR = 1.37, 95 % CI = 1.11-1.70, P = 0.004). There was no significant association found between A1298C polymorphism and breast cancer risk under all genetic models (C vs. A: OR = 0.96, 95 % CI = 0.89-1.03, P = 0.268; CC vs. AA: OR = 0.98, 95 % CI = 0.77-1.26, P = 0.899; AC vs. AA: OR = 0.95, 95 % CI = 0.88-1.02, P = 0.174; CC vs. AC/AA: OR = 1.00, 95 % CI = 0.78-1.28, P = 0.996, CC/AC vs. AA: OR = 0.96, 95 % CI = 0.89-1.02, P = 0.196). In summary, during this meta-analysis, we found that MTHFR C677T polymorphism was significantly associated with breast cancer risk in the Chinese population. Meanwhile, MTHFR A1298C polymorphism was not associated with breast cancer risk in the Chinese population.