Known modifiable risk factors account for a small fraction of premenopausal breast
cancers. We investigated associations between pre-diagnostic circulating
amino acid and
amino acid-related metabolites (N = 207) and risk of
breast cancer among predominantly premenopausal women of the Nurses' Health Study II using conditional logistic regression (1057 cases, 1057 controls) and multivariable analyses evaluating all metabolites jointly. Eleven metabolites were associated with
breast cancer risk (q-value < 0.2). Seven metabolites remained associated after adjustment for established risk factors (p-value < 0.05) and were selected by at least one multivariable modeling approach: higher levels of
2-aminohippuric acid,
kynurenic acid,
piperine (all three with q-value < 0.2), DMGV and
phenylacetylglutamine were associated with lower
breast cancer risk (e.g.,
piperine: ORadjusted (95%CI) = 0.84 (0.77-0.92)) while higher levels of
creatine and C40:7
phosphatidylethanolamine (PE)
plasmalogen were associated with increased
breast cancer risk (e.g., C40:7 PE
plasmalogen: ORadjusted (95%CI) = 1.11 (1.01-1.22)). Five
amino acids and
amino acid-related metabolites (2-
aminohippuric acid, DMGV,
kynurenic acid,
phenylacetylglutamine, and
piperine) were inversely associated, while one
amino acid and a
phospholipid (
creatine and C40:7 PE
plasmalogen) were positively associated with
breast cancer risk among predominately premenopausal women, independent of established
breast cancer risk factors.