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Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II

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Abstract

Purpose

Prior prospective studies, including our own, have evaluated total plasma 25-hydroxyvitamin D [25(OH)D] and breast cancer risk with inconsistent results. However, recent studies suggest that some vitamin D functions may be more relevant to the unbound (free) fraction of 25(OH)D. Vitamin D binding protein (DBP) influences the free 25(OH)D levels and thus possibly the biological activities of vitamin D.

Methods

We conducted a case–control study nested within the Nurses’ Health Study II to evaluate the association of plasma free 25(OH)D and DBP with breast cancer risk in predominantly premenopausal women. Plasma samples were assayed for 25(OH)D and DBP in 584 case–control pairs. Free 25(OH)D levels were calculated based on plasma levels of total 25(OH)D, DBP, and a constant value representing average albumin levels. Conditional logistic regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs).

Results

We found no association between plasma calculated free 25(OH)D and risk of breast cancer overall (highest vs. lowest quartile RR 1.21, 95 % CI 0.83–1.77, trend test p value = 0.50). No association was observed for plasma DBP as well (highest vs. lowest quartile RR 0.95, 95 % CI 0.67–1.36, trend test p value = 0.96). Results were similar by tumor hormone receptor status. Neither the total nor the calculated free 25(OH)D and breast cancer association substantially varied by plasma DBP levels.

Conclusions

Our study does not support an important role of either calculated circulating free 25(OH)D or circulating DBP levels in breast cancer risk among predominantly premenopausal women.

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Abbreviations

25(OH)D:

25-Hydroxyvitamin D

DBP:

Vitamin D binding protein

VDR:

Vitamin D receptor

1,25(OH)2D3 :

1,25-Dihydroxyvitamin D3

NHS:

Nurses’ Health Study

CV:

Coefficient of variation

ER:

Estrogen receptor

PR:

Progesterone receptor

BMI:

Body mass index

RR:

Relative risk

CI:

Confidence interval

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Acknowledgments

This study was supported by Research Grants CA67262 and CA50385 from the National Cancer Institute. We would like to thank the participants and staff of the Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY,LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Conflict of interest

All authors disclosed no potential conflict of interest.

Author information

Authors and Affiliations

  1. Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 N. Pleasant Street, Amherst, MA, 01003, USA

    Jun Wang & Susan E. Hankinson

  2. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA, 02115, USA

    A. Heather Eliassen, Walter C. Willett & Susan E. Hankinson

  3. Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    A. Heather Eliassen, Donna Spiegelman, Walter C. Willett & Susan E. Hankinson

  4. Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Donna Spiegelman

  5. Department of Nutrition, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA

    Walter C. Willett

Authors
  1. Jun Wang
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  2. A. Heather Eliassen
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  3. Donna Spiegelman
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Correspondence to Jun Wang.

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Wang, J., Eliassen, A.H., Spiegelman, D. et al. Plasma free 25-hydroxyvitamin D, vitamin D binding protein, and risk of breast cancer in the Nurses’ Health Study II. Cancer Causes Control 25, 819–827 (2014). https://doi.org/10.1007/s10552-014-0383-5

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  • DOI: https://doi.org/10.1007/s10552-014-0383-5

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