Plasma metabolomic signature of a proinflammatory diet in relation to breast cancer risk: a prospective cohort study.

BACKGROUND

A proinflammatory diet has been linked to an increased risk of breast cancer. However, the underlying metabolic roles remain to be elucidated.

OBJECTIVES

This study aimed to investigate the metabolic mechanism between proinflammatory diet and breast cancer risk.

METHODS

This prospective study included 273,324 females from the UK Biobank. The dietary inflammatory potential was assessed via an energy-adjusted dietary inflammatory index (E-DII) based on a 24-h recall questionnaire. The plasma metabolome was profiled via high-throughput nuclear magnetic resonance spectroscopy. A metabolic signature was constructed by summing selected metabolite concentrations weighted by the coefficients via absolute shrinkage and selection operator analysis. Multivariate Cox regression was applied to assess the associations of the E-DII and metabolic signature with breast cancer risk.

RESULTS

We constructed a metabolic signature comprising 26 metabolites associated with a proinflammatory diet. These metabolites primarily included lipoproteins, amino acids, fatty acids, and ketone bodies. Both the E-DII and metabolic signature were positively associated with breast cancer risk [hazard ratio (HR) comparing the highest quintile with the lowest quintile: 1.17; 95% CI: 1.04, 1.32; and 1.21; 95% CI: 1.01, 1.46, respectively]. Furthermore, we found that saturated fatty acids to total fatty acids percentage and acetone concentration were positively associated (HR: 1.20; 95% CI: 1.04, 1.37; HR: 1.15; 95% CI: 1.01, 1.32, respectively), whereas the degree of unsaturation was inversely associated with breast cancer risk (HR: 0.86; 95% CI: 0.75, 0.99).

CONCLUSIONS

We identified a metabolic signature that reflects a proinflammatory diet and is associated with increased risk of breast cancer.