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01-07-2019 | Breast Cancer | Epidemiology

Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women

Authors: Serena C. Houghton, A. Heather Eliassen, Shumin M. Zhang, Jacob Selhub, Bernard A. Rosner, Walter C. Willett, Susan E. Hankinson

Published in: Breast Cancer Research and Treatment | Issue 1/2019

Abstract

Purpose

We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women.

Methods

We conducted a nested case–control study within the Nurses’ Health Study II. From blood samples collected in 1996–1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics.

Results

Plasma vitamin B₁₂ was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29, p-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (p-interaction < 0.05).

Conclusions

Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.

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Title: Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women
Authors: Serena C. Houghton
A. Heather Eliassen
Shumin M. Zhang
Jacob Selhub
Bernard A. Rosner
Walter C. Willett
Susan E. Hankinson
Publication date: 01-07-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 1/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05223-x

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