Multi-metabolite scores of alignment with the 2018 World Cancer Research Fund (WCRF)/ American Institute for Cancer Research (AICR) Cancer Prevention Recommendations in the Interactive Diet and Activity Tracking in AARP (IDATA) Study.

Authors

Malcomson FC, Lee SK, O'Connell CP, Shams-White MM, Reedy J, Playdon MC, Tabung FK, Watts EL, Moore SC, Hong HG, Loftfield E

Affiliations

• Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA; Human Nutrition & Exercise Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK; Centre for Cancer, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
• Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
• Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
• Population Science, American Cancer Society, Atlanta, GA, USA.
• Risk Factor Assessment Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD, USA.
• Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA; Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.
• Department of Internal Medicine, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH, USA.
• Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. Electronic address: erikka.loftfield@nih.gov.

Abstract

BACKGROUND: 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.

OBJECTIVE: This study aimed to identify multi-metabolite scores of alignment with the Cancer Prevention Recommendations in three biospecimens collected from Interactive Diet and Activity Tracking in AARP (IDATA) Study participants.

METHODS: 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-hour 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 super-pathways and sub-pathways.

RESULTS: IDATA Study participants with complete data (n=638) were included (mean age 63.1 years, 50% female). 2018 WCRF/AICR Score was associated with 399 metabolites in serum (r range -0.32-0.36), 464 in 24-hour (r range -0.32-0.37), and 349 in FMV urine (r range -0.29-0.31) (FDR-adjusted P<0.05). LASSO regression selected 36 metabolites in serum, 17 in 24-hour 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.

CONCLUSIONS: 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 multi-metabolite scores may serve as objective indicators of a healthier lifestyle in studies of cancer and related outcomes.