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Abstract 5042: Folate and other B-vitamins and the risk of breast cancer in younger women

Purpose: Prior epidemiologic cohort studies have generally found no associations of folate and other B-vitamins with breast cancer overall, but differences by menopause status have been suggested. However, prior studies have been limited by small numbers to examine the relationship between different plasma measures and related polymorphisms and breast cancer risk among younger women. Therefore, we examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women. Methods: We conducted a nested case-control study within the Nurses’ Health Study II. From blood samples collected in 1996-1999 and follow-up through 2007, plasma measures were available for 610 cases and 1,207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics. Results: Plasma vitamin B12 was associated with a 71% increase in risk of breast cancer comparing the highest versus lowest quintile (95%CI=1.22-2.39, p-trend=0.02). Plasma folate (comparable RR=1.20, 95%CI=0.85-1.68), pyridoxal 5’-phosphate (RR=1.19, 95%CI=0.85-1.65), cysteine (RR=1.15, 95%CI=0.81-1.63), homocysteine (RR=0.90, 95%CI=0.65-1.25), and cysteinylglycine (RR=0.92, 95%CI=0.65-1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive (RR highest tertile vs. lowest=1.48, 95%CI=1.09-2.01) and estrogen receptor-positive/progesterone receptor-positive breast cancer (RR T3 vs. T1= 1.59, 95%CI= 1.12-2.27) and the invasive association was suggestively stronger for bloods collected post-fortification (p-heterogeneity=0.19). Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use and MTHFR status (p-interaction Conclusions: Overall, plasma B-vitamins and metabolites were not consistently associated with lower breast cancer risk. For increasing plasma folate and B12 levels higher risk of invasive breast cancer was observed. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Future studies in younger women are needed to confirm findings. Citation Format: Serena C. Houghton, A Heather Eliassen, Shumin Zhang, Jacob Selhub, Bernard A. Rosner, Walter C. Willett, Susan E. Hankinson. Folate and other B-vitamins and the risk of breast cancer in younger women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5042.