Plasma B-vitamins and one-carbon metabolites and the risk of breast cancer in younger women

Purpose 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 1207 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 B 12 was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17–2.29, p -trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84–1.66), pyridoxal 5′-phosphate (RR = 1.18, 95% CI 0.85–1.64), homocysteine (RR = 0.93, 95% CI 0.67–1.28), cysteine (RR = 1.14, 95% CI 0.81–1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66–1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status ( p -interaction