ArticleEuropean journal of clinical nutrition2020
Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study.
Article in European journal of clinical nutrition, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Biological, dietetic and pharmacological properties of vitamin BNPJ science of food · 2025Review
- Plasma One-Carbon Metabolism-Related Micronutrients and the Risk of Breast Cancer: Involvement of DNA Methylation.Nutrients · 2023Article
- Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesFolates found in natural foods are thought to protect against cancer. However, folic acid (FA), a synthetic form of folate used in supplements and fortified foods, may increase breast cancer risk if present in unmetabolized form (UMFA) in the circulation. This study examined the associations of serum UMFA and 5-methyltetrahydrofolate (5-mTHF), the predominant form of circulating folate, with breast cancer risk. SUBJECTS/
methodsWe conducted a nested case-control study in a prospective cohort. In total, 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1059 controls. Serum UMFA and 5-mTHF were measured using liquid chromatography-tandem mass spectrometry in stored serum samples, and 5-mTHF was corrected for storage degradation.
resultsSerum UMFA was not associated with breast cancer risk: the percentage of women with detectable levels of UMFA was similar in cases and controls (18% and 20%, respectively; p = 0.46). Two tag-SNPs in the promoter region of the FA-metabolizing gene were also not associated with risk. There was a marginally significant inverse association of 5-mTHF
conclusionsCirculating UMFA was not associated with breast cancer risk. These results apply to countries without mandatory FA food fortification. Studies are needed in countries with mandatory fortification, where levels of UMFA are much higher than in our study.
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