ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2025
Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dietary inflammatory index and the risk of colorectal adenomas and cancer: a systematic review and dose-response meta-analysis.Nutrition journal · 2025Pooled it
- Plasma metabolites, metabolic risk score and colorectal cancer risk: a prospective cohort study.European journal of epidemiology · 2025Article
- Microbiome as a predictive biomarker in locally advanced rectal cancer.Microbiome research reports · 2025Article
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Authors and funding
29 authors.
Funding
Abstract
backgroundCurrent evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer. However, the mediating role of the circulating metabolome in this relationship remains unclear.
methodsTargeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case-control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA-colorectal cancer association.
resultsPA was inversely associated with colorectal cancer risk (OR per category change: 0.90, 95% confidence interval, 0.83-0.97; P value = 0.009). PA levels were associated with 24 circulating metabolites after FDR correction, with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted P value = 1.18 × 10-10) and lysophosphatidylcholine acyl C18:2 (FDR-adjusted P value = 1.35 × 10-6). PC ae C34:3 partially mediated the PA-colorectal cancer association (natural indirect effect: 0.991, 95% confidence interval, 0.982-0.999; P value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature.
conclusionsPC ae C34:3 mediates part of the PA-colorectal cancer inverse association, but further studies with improved PA measures and extended metabolomic panels are needed. IMPACT: These findings provide insights into PA-related biological mechanisms influencing colorectal cancer risk and suggest potential targets for cancer prevention interventions.
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