Physical Activity, Metabolites, And Breast Cancer Associations

PURPOSE: To investigate the associations between physical activity and metabolites, and their relationship with breast cancer risk. METHODS: Total physical activity was assessed using four measures, doubly labelled water (physical activity level), ActiGraph (MET hrs/day), activPAL (step count) and ACT24 questionnaires (MET hrs/day). Each assessment occurred 1-6 times over a 12-month period. Blood samples were also collected to quantify metabolite concentrations. We used partial Spearman correlations to assess associations between total physical activity and 1,033 serum metabolites, and we corrected for multiple testing using the false discovery rate (p-adj < 0.05). Associations between physical activity associated metabolites and breast cancer risk were analyzed in a nested case control subset in a prospective cohort (PLCO: 621 cases and 621 controls) using conditional logistic regression. RESULTS: IDATA participants were aged 50-74 years (mean = 63 years) and 51% were women. We identified 149 serum metabolites associated with any of the four physical activity measures. These metabolites spanned a wide range of metabolic pathways, particularly amino acids and fatty acid metabolism, and energy production. There was limited agreement between metabolites associated with each physical activity measure, with only 1-methylnicotinamide associated with all four physical activity measures (r = 0.11-0.16), which could suggest differences in biological effects. Ninety-two of the physical activity-associated metabolites were also measured in PLCO, of which 8 were associated with breast cancer risk. Seven of these were consistent with a protective effect of physical activity on breast cancer risk, namely 2-methylbutyroylcarnitine, isovalerylglycine, and N-acetyltaurine (amino acids), androsterone sulfate and octadecanedioic acid (lipids), cytidine (nucleotide) and X-21410 (unclassified). These metabolites particularly implicated a role for the leucine, isoleucine, and valine metabolism in explaining the protective role of physical activity on breast cancer risk. CONCLUSIONS: Physical activity is associated with a broad range of metabolites, some of which are also associated with reduced breast cancer risk, highlighting potential metabolic pathways for cancer prevention. NIH Intramural Research Program