Association Between One-carbon Metabolism-related Vitamins and Risk of Breast Cancer: A Systematic Review and Meta-analysis of Prospective Studies

Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B-6, vitamin B-2, vitamin B-12) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B-6, and vitamin B-2 might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B12 and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B6 might decrease the risk of estrogen receptor-negative (ER-)/progesterone receptornegative (PR-) breast cancer but not ER+/PR+ breast cancer. The doseeresponse meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER-/PR- breast cancer. An increment of folate intake (100 mg/d) corresponded to a 7% deceased risk of ER-/PR- breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER-/PR- breast cancer. (C) 2020 Elsevier Inc. All rights reserved.