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Int J Cancer. 2019 Apr 15;144(8):1929-1940. doi: 10.1002/ijc.31934. Epub 2019 Jan 3.

Plasma B-vitamin and one-carbon metabolites and risk of breast cancer before and after folic acid fortification in the United States.

Author information

1
Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA.
2
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
3
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
4
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
5
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
6
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
7
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

Abstract

Prior epidemiologic findings for plasma folate and B-vitamins and breast cancer risk are inconsistent and have not assessed the influence of folic acid fortification. Therefore, we examined the associations of plasma folate, B12 , pyridoxal 5'-phosphate (PLP), homocysteine, cysteine and cysteinylglycine with breast cancer risk, before and after fortification. We conducted a nested case-control study within the prospective Nurses' Health Study. In 1989-1990 (pre-fortification), 32,826 women donated a blood sample and 18,743 donated an additional blood sample in 2000-2001 (post-fortification). Between the first blood collection and 2006, 1874 incident breast cancer cases with at least one blood sample and 367 with two were 1:1 matched to controls. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors. Overall, higher plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine levels were not associated with breast cancer risk. Associations did not vary by in situ/invasive, hormone receptor status, or tumor molecular subtype. Additionally, associations were null before and after fortification. For example, the RR (95% CI) for the highest versus lowest tertile of 1990 (pre-fortification) plasma folate with 1990-2000 follow-up was 0.93 (0.75-1.16) and for the 2000 plasma folate (post-fortification) with 2000-2006 follow-up the RR (95% CI) was 1.17 (0.79-1.74). Plasma folate, B12 , PLP, homocysteine, cysteine and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific tumor molecular subtypes. However, long term associations (>8 years) after the implementation of fortification could not be examined.

KEYWORDS:

breast cancer; folic acid fortification; molecular subtypes; plasma B-vitamins; plasma Folate

PMID:
30346061
DOI:
10.1002/ijc.31934
[Indexed for MEDLINE]

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