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

  • Shana J. Kim
  • Cindy X. W. Zhang
  • Rochelle Demsky
  • Susan Armel
  • Young-In Kim
  • Steven A. Narod
  • Joanne KotsopoulosEmail author



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.


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.


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).


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.


Folic acid Multivitamin Supplements BRCA Breast cancer 



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.

Compliance with ethical standards

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.

Supplementary material

10549_2018_5118_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Women’s College HospitalWomen’s College Research InstituteTorontoCanada
  2. 2.Department of Nutritional SciencesUniversity of TorontoTorontoCanada
  3. 3.Department of Medical SciencesUniversity of WesternLondonCanada
  4. 4.Department of Molecular GeneticsUniversity of TorontoTorontoCanada
  5. 5.Division of Gynecologic Oncology, Princess Margaret HospitalUniversity Health NetworkTorontoCanada
  6. 6.Department of MedicineUniversity of TorontoTorontoCanada
  7. 7.Keenan Research Centre for Biomedical Science of St. Michael’s HospitalSt. Michael’s HospitalTorontoCanada
  8. 8.Division of GastroenterologySt. Michael’s HospitalTorontoCanada
  9. 9.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada

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