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Folate Intake and the Risk of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies

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  • Yu-Fei Zhang
  • Wei-Wu Shi
  • Hong-Fang Gao
  • Li Zhou
  • An-Ji Hou
  • Yu-Hao Zhou

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. Methodology and Principal Findings: 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. Conclusion/Significance: 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.

Suggested Citation

  • Yu-Fei Zhang & Wei-Wu Shi & Hong-Fang Gao & Li Zhou & An-Ji Hou & Yu-Hao Zhou, 2014. "Folate Intake and the Risk of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-11, June.
    • Handle: RePEc:plo:pone00:0100044
    DOI: 10.1371/journal.pone.0100044
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    References listed on IDEAS

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    1. Nicola Orsini & Rino Bellocco & Sander Greenland, 2006. "Generalized least squares for trend estimation of summarized dose–response data," Stata Journal, StataCorp LP, vol. 6(1), pages 40-57, March.
    2. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
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    Cited by:

    1. María Morales-Suárez-Varela & Amparo Ruiz Simon & Salvador Blanch Tormo & Ismael Pastor Climente & Maximino Redondo Bautista & Isabel Peraita-Costa & Agustin Llopis-Morales & Agustin Llopis-Gonzalez, 2020. "Effect of Breast Cancer Treatment on Dietary Vitamin Intake Levels," IJERPH, MDPI, vol. 18(1), pages 1-17, December.
    2. Bijing Mao & Yafei Li & Zhimin Zhang & Chuan Chen & Yuanyuan Chen & Chenchen Ding & Lin Lei & Jian Li & Mei Jiang & Dong Wang & Ge Wang, 2015. "One-Carbon Metabolic Factors and Risk of Renal Cell Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-10, October.

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