Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk: a meta-analysis from 41 studies with 16,480 cases and 22,388 controls.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely reported, but results were inconsistent and underpowered. To clarify the effects of MTHFR polymorphisms on the risk of breast cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of 41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009-1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019-1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014-1.236); in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016-1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073-1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058-1.513) but not in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found. With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity- and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play a low penetrance role in the development of breast cancer.