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Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case–control study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Supplemental folic acid (the more bioavailable and synthetic form of folate) and breast cancer risk in BRCA mutation carriers have not been studied. We evaluated folic acid, vitamin B6 and vitamin B12 supplement use, and breast cancer risk among BRCA mutation carriers.

Methods

In this case–control study, dietary supplement use was collected from BRCA mutation carriers living in Canada. Supplement use was categorized as never or ever use. Total average daily supplement use was categorized as never, moderate, and high use based on tertiles. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for supplement use and breast cancer risk.

Results

We included 129 breast cancer cases and 271 controls. Women who used any folic acid-containing supplement had a significantly decreased risk of breast cancer compared to women who never used a folic acid-containing supplement (OR 0.45; 95%CI 0.25, 0.79; P = 0.006). This was significant for BRCA1 mutation carriers only. The OR for moderate folic acid supplement intake was 0.39; P = 0.01, and high intake was 0.54; P = 0.09, compared to never users. Moderate vitamin B12 supplement intake was associated with decreased risk of breast cancer compared to never use (OR 0.48; 95%CI 0.24, 0.96; P = 0.04).

Conclusions

In this first investigation of folic acid supplement use and breast cancer risk in BRCA mutation carriers, these findings suggest that moderate folic acid- and vitamin B12-containing supplement use may be protective for BRCA-associated breast cancer, particularly among BRCA1 mutation carriers. Future studies with larger samples and prospective follow-up are needed.

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Funding

This study was funded by the Champions of Genetics Grant from the Canadian Gene Cure Foundation in partnership with the CIHR Institute of Genetics and Canadian Cancer Society Research Institute (703058). SJK was supported by a Province of Ontario Graduate Scholarship and the Enid Walker Graduate Student Award in Women’s Health Research. JK is the recipient of a Canada Research Chair, tier II, and SAN is the recipient of a Canada Research Chair, tier I.

Author information

Authors and Affiliations

  1. Women’s College Hospital, Women’s College Research Institute, 76 Grenville St., 6th Floor, Toronto, ON, M5S 1B2, Canada

    Shana J. Kim, Steven A. Narod & Joanne Kotsopoulos

  2. Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada

    Shana J. Kim, Young-In Kim, Steven A. Narod & Joanne Kotsopoulos

  3. Department of Medical Sciences, University of Western, London, ON, Canada

    Cindy X. W. Zhang

  4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Rochelle Demsky & Susan Armel

  5. Division of Gynecologic Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada

    Rochelle Demsky & Susan Armel

  6. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Young-In Kim & Steven A. Narod

  7. Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, St. Michael’s Hospital, Toronto, ON, Canada

    Young-In Kim

  8. Division of Gastroenterology, St. Michael’s Hospital, Toronto, ON, Canada

    Young-In Kim

  9. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Steven A. Narod & Joanne Kotsopoulos

Authors
  1. Shana J. Kim
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  2. Cindy X. W. Zhang
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  3. Rochelle Demsky
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  4. Susan Armel
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  5. Young-In Kim
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  6. Steven A. Narod
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  7. Joanne Kotsopoulos
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Corresponding author

Correspondence to Joanne Kotsopoulos.

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Conflict of interest

The authors declare no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Kim, S.J., Zhang, C.X.W., Demsky, R. et al. Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case–control study. Breast Cancer Res Treat 174, 741–748 (2019). https://doi.org/10.1007/s10549-018-05118-3

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  • DOI: https://doi.org/10.1007/s10549-018-05118-3

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