Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship

Background: Current 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.Methods: Targeted metabolomics data from 6,055 participants in the Europe...

ver descrição completa

Detalhes bibliográficos
Autores: Papadimitriou, Nikos, Kazmi, Nabila, Tsilidis, Konstantinos K., Richmond, Rebecca C., Lynch, Brigid M., Bendinelli, Benedetta, Ricceri, Fulvio, Sánchez Pérez, María José, Trobajo-sanmartin, Camino, Jakszyn, Paula, Simeon, Vittorio, Severi, Gianluca, Perduca, Vittorio, Truong, Thérèse, Ferrari, Pietro, Keski-Rahkonen, Pekka, Weiderpass, Elisabete, Eichelmann, Fabian, Schulze, Matthias B., Katzke, Verena, Fortner, Renée T., Heath, Alicia K., Aune, Dagfinn, Harewood, Rhea, Dahm, Christina C., Aginagalde Llorente, Adrian Hugo, Gunter, Marc J., Murphy, Neil, Lewis, Sarah J.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221595
Acesso em linha:https://hdl.handle.net/2445/221595
Access Level:acceso abierto
Palavra-chave:Càncer colorectal
Metabolòmica
Colorectal cancer
Metabolomics
Descrição
Resumo:Background: Current 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.Methods: Targeted 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.Results: PA 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 x 10-10) and lysophosphatidylcholine acyl C18:2 (FDR-adjusted P value = 1.35 x 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.Conclusions: PC 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.

Registos relacionados