1. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study
- Author
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Tess V. Clendenen, Yelena Afanasyeva, Karen L. Koenig, Stephanie Scarmo, Anne Zeleniuch-Jacquotte, and Per Magne Ueland
- Subjects
0301 basic medicine ,Fortification ,Medicine (miscellaneous) ,Physiology ,Breast Neoplasms ,030209 endocrinology & metabolism ,Article ,03 medical and health sciences ,Folic Acid ,0302 clinical medicine ,Breast cancer ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Tetrahydrofolates ,030109 nutrition & dietetics ,Nutrition and Dietetics ,business.industry ,Food fortification ,Cancer ,Odds ratio ,medicine.disease ,Folic acid ,Case-Control Studies ,Nested case-control study ,Female ,business - Abstract
BACKGROUND/OBJECTIVES: Folates 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/METHODS: We conducted a nested case-control study in a prospective cohort. 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1,059 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. RESULTS: Serum 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(corrected) with breast cancer risk (odds ratio for the highest vs. lowest quintile = 0.69, 95% CI = 0.49 to 0.97; p(trend) = 0.08). CONCLUSION: Circulating 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.
- Published
- 2020