Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case–control study
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.
KeywordsFolic 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.
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 was obtained from all individual participants included in the study.
- 2.Centers for Disease Control and Prevention (2018) Folic acid recommendations. http://www.cdc.gov/ncbddd/folicacid/recommendations.html. Accessed 5 Sept 2018
- 3.Health C (2013) Prenatal Nutrition Guidelines for Health Professionals-Folate Contributes to a Healthy Pregnancy. http://www.hc-sc.gc.ca/fn-an/pubs/nutrition/folate-eng.php. Accessed 5 Sept 2018
- 4.World Health Organization. Daily iron and folic acid supplementation in pregnant women. http://www.who.int/nutrition/publications/micronutrients/guidelines/summary_guideline_daily_ifa_supp_pregnant_women.pdf?ua=1. Accessed 5 Sept 2018
- 11.Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130CrossRefGoogle Scholar
- 19.Zhang Z (2016) Missing data imputation: focusing on single imputation. Ann Transl Med 4(1):9Google Scholar
- 24.Shiovitz S, Korde LA (2015) Genetics of breast cancer: a topic in evolution. Ann Oncol 26(7):1291–1299Google Scholar