title: Folate intake and the risk of breast cancer: a dose-response meta-analysis of prospective studies.
abstract: BACKGROUND
  Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach.
  
  
  RESULTS
  We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97; 95% CI, 0.90-1.05; P = 0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98-1.01; P = 0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007) and revealed that a daily folate intake of 200-320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg.
  
  
  CONCLUSIONS
  Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.
authors.affiliation: Department of Oncology, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical College, Linhai, Zhejiang, China.
authors.forename: Wei-Wu
authors.initials: WW
authors.lastname: Shi
authors.affiliation: Department of Oncology, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Gao
authors.affiliation: Department of Oncology, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: An-Ji
authors.initials: AJ
authors.lastname: Hou
authors.affiliation: Department of Rehabilitation Institute, Shanghai Seventh People's Hospital, Shanghai, China.
authors.forename: Yu-Hao
authors.initials: YH
authors.lastname: Zhou
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D064887:Observational Studies as Topic; D011446:Prospective Studies; D012307:Risk Factors; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid