Multi-metabolite Scores of Alignment with the 2018 World Cancer Research Fund/American Institute for Cancer Research...

Lifestyle patterns, such as following the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations, may modulate cancer risk through changes to metabolites, which reflect exposure to certain foods or changes in metabolism that impact biological processes.

This study aimed to identify multimetabolite scores of alignment with the Cancer Prevention Recommendations in 3 biospecimens collected from Interactive Diet and Activity Tracking (IDATA) in American Association of Retired Persons study participants.

Dietary, alcohol, physical activity, and anthropometric data were used to estimate alignment with the Cancer Prevention Recommendations using the standardized 2018 WCRF/AICR Score. Metabolites were measured in serum, first morning void (FMV), and 24-h urine by Metabolon, Inc., using ultrahigh-performance liquid chromatography with tandem mass spectrometry. Partial Spearman correlations were used to estimate pairwise associations between 2018 WCRF/AICR Score and 852 metabolites in serum and 934 metabolites in urine. Least absolute shrinkage and selection operator (LASSO) regression identified a subset of metabolites jointly associated with the score. Enrichment analysis identified associated metabolite superpathways and subpathways.

IDATA study participants with complete data (n = 638) were included (mean age 63.1 y, 50% female). 2018 WCRF/AICR Score was associated with 399 metabolites in serum (r range: -0.32 to 0.36), 464 in 24-h (r range: -0.32 to 0.37), and 349 in FMV urine (r range: -0.29 to 0.31) (false discovery rate-adjusted P < 0.05). LASSO regression selected 36 metabolites in serum, 17 in 24-h and 17 in FMV urine. Identified metabolites spanned a range of chemical classes, including amino acid, vitamin and lipid metabolism, as well as food component and plant metabolites.

Greater alignment with the Cancer Prevention Recommendations was associated with metabolites related to a range of cellular functions and pathways, providing insight into potential mechanisms. The identified multimetabolite scores may serve as objective indicators of a healthier lifestyle in studies of cancer and related outcomes. The IDATA study was approved by the National Cancer Institute Special Studies Institutional Review Board (IRB approval number 11CN155) and is registered at clinicaltrials.gov as NCT03268577.