2026-04-14T04:50:00Zhttps://recercat.cat/oai/requestoai:recercat.cat:20.500.14342/52492025-04-30T19:06:06Zcom_2072_482405com_2072_183628col_2072_482409
2025-04-30T19:06:05Z
urn:hdl:20.500.14342/5249
Identifying metabolomic mediators of the physical activity and colorectal cancer relationship
Papadimitriou, Nikos
Kazmi, Nabila
Tsilidis, Konstantinos K.
Richmond, Rebecca C.
Lynch, Brigid M.
Bendinelli, Benedetta
Ricceri, Fulvio
Sánchez, Maria Jose
Trobajo-Sanmartín, Camino
Jakszyn, Paula
Simeon, Vittorio
Severi, Gianluca
Perduca, Vittorio
Truong, Therese
Ferrari, Pietro
Keski-Rahkonen, Pekka
Weiderpass, Elisabete
Eichelmann, Fabian
Schulze, Matthias B.
Katzke, Verena Andrea
Turzanski‑Fortner, Renée
Heath, Alicia K.
Aune, Dagfnn
Harewood, Rhea
Dahm, Christina C.
Llorente, Adrian
Gunter, Marc J.
Murphy, Neil
Lewis, Sarah Jayne
Metabolòmica
Exercici
Còlon -- Càncer
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 × 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.
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.
2025-04-30T19:06:05Z
2025-04-30T19:06:05Z
2024-09
2025-04
info:eu-repo/semantics/article
http://hdl.handle.net/20.500.14342/5249
https://doi.org/10.1158/1055-9965.EPI-24-1390
eng
Cancer epidemiology, biomarkers and prevention, 2025, 34(4): 578-587
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
© L'autor/a
Attribution-NonCommercial-NoDerivatives 4.0 International
American Association for Cancer Research