Abstract LB-185: The effects of plasma folate and other B vitamins on breast cancer risk in BRCA1 and BRCA2 mutation carriers
Authors: Kim Shana J. , Zuchniak Anna , Kim Young-In , Lamers Yvonne , Kotsopoulos Joanne , Narod Steven 
Published: August 2015

Background: Women who inherit a deleterious BRCA mutation face a high lifetime risk of developing breast cancer, estimated at 80% compared with 11% in the general population.

Current prevention options are limited to prophylactic surgery (removal of the breast and/or ovaries) and/or chemoprevention. Nonsurgical prevention options including dietary and lifestyle recommendations are highly desired by this population but have yet to be elucidated. Folate and other B-vitamins involved in folate metabolism are of particular interest given their essential roles in DNA synthesis and maintaining genomic stability, the reported dual effects on carcinogenesis (promoting or preventing), and the high levels of intake due to mandatory food fortification and supplement use. Given the heightened predisposition for cancer development among BRCA mutation carriers, clarifying the role of these nutrients on breast cancer development in this population is of extreme importance.

Objectives: To prospectively investigate the relationship between plasma folate, B12 and B6 levels and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.

Methods: We included 169 Canadian women who provided a blood sample at enrollment and had no history of cancer from an on-going international cohort of BRCA mutation carriers, the Risk Factor Analysis of Hereditary Breast and Ovarian Cancer Study. Baseline and biennial follow-up questionnaires collected relevant information regarding family, reproductive and medical histories, selected lifestyle factors, and disease incidence. Plasma folate and B12 levels were determined with microbiological microtitre assays, methylmalonic acid (MMA, a functional biomarker of vitamin B12) was quantified using reversed-phase LC-tandem mass spectrometry, and pyridoxal 5′-phosphate (PLP) measuring active B6 was determined with a non-radioactive apo-enzymatic assay. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals.

Results: During a mean follow-up of 8 years, 21 women were diagnosed with invasive breast cancer. At baseline, the participants had a mean age of 52.7 ± 12.2 years and BMI of 25.0 ± 5.0 kg/m2. The mean plasma folate level was 17.8 ng/mL ± 11.9, ranging from 0.24 to 68.5 ng/mL. Unaffected women had an average plasma folate level of 21.7 ng/mL compared to 19.2 ng/mL in affected women (P = 0.46). Plasma B12 and B6 assays are currently underway. Results from statistical analyses are expected in March 2015.

Impact: To our knowledge, this represents the first prospective study evaluating the effect of folate and other B vitamins on the risk of breast cancer among women with a BRCA1 or BRCA2 mutation. The results from this study will help develop safe and targeted recommendations for prevention in genetically predisposed women.

Funding: Canadian Institutes of Health Research, Canadian Gene Cure Foundation.

Citation Format: Shana J. Kim, Anna Zuchniak, Young-In Kim, Yvonne Lamers, Joanne Kotsopoulos, Steven Narod. The effects of plasma folate and other B vitamins on breast cancer risk in BRCA1 and BRCA2 mutation carriers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2015-LB-185