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000298365 1001_ $$00000-0001-8294-7262$$aPapadimitriou, Nikos$$b0
000298365 245__ $$aIdentifying metabolomic mediators of the physical activity and colorectal cancer relationship.
000298365 260__ $$aPhiladelphia, Pa.$$bAACR$$c2025
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000298365 520__ $$aCurrent evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer (CRC). However, the mediating role of the circulating metabolome in this relationship remains unclear.Targeted metabolomics data from 6,055 participants in the EPIC 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-CRC association.PA was inversely associated with CRC risk (odds ratio [OR] per category change: 0.90, 95% confidence intervals [CI]: 0.83, 0.97; p-value = 0.009). PA levels were associated with 24 circulating metabolites after false discovery rate correction (FDR), with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted p-value = 1.18 × 10⁻¹⁰) and lysophosphatidylcholine acyl (lysoPC a) C18:2 (FDR-adjusted p-value = 1.35 × 10⁻⁶). PC ae C34:3 partially mediated the PA-CRC association (natural indirect effect: 0.991, 95% CI: 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.PC ae C34:3 mediates part of the PA-CRC inverse association, but further studies with improved PA measures and extended metabolomic panels are needed.These findings provide insights into PA-related biological mechanisms influencing CRC risk and suggest potential targets for cancer prevention interventions.
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000298365 7001_ $$00009-0007-6876-5324$$aKazmi, Nabila$$b1
000298365 7001_ $$00000-0002-8452-8472$$aTsilidis, Konstantinos K$$b2
000298365 7001_ $$00000-0003-0574-5071$$aRichmond, Rebecca C$$b3
000298365 7001_ $$00000-0001-8060-547X$$aLynch, Brigid M$$b4
000298365 7001_ $$00000-0002-4796-1517$$aBendinelli, Benedetta$$b5
000298365 7001_ $$00000-0001-8749-9737$$aRicceri, Fulvio$$b6
000298365 7001_ $$00000-0003-4817-0757$$aSánchez, Maria-Jose$$b7
000298365 7001_ $$00000-0001-5105-252X$$aTrobajo-Sanmartín, Camino$$b8
000298365 7001_ $$00000-0003-0672-8847$$aJakszyn, Paula$$b9
000298365 7001_ $$00000-0003-2387-4125$$aSimeon, Vittorio$$b10
000298365 7001_ $$00000-0001-7157-419X$$aSeveri, Gianluca$$b11
000298365 7001_ $$00000-0003-0339-0473$$aPerduca, Vittorio$$b12
000298365 7001_ $$00000-0002-2943-6786$$aTruong, Therese$$b13
000298365 7001_ $$00000-0001-9358-7338$$aFerrari, Pietro$$b14
000298365 7001_ $$00000-0001-9437-3040$$aKeski-Rahkonen, Pekka$$b15
000298365 7001_ $$00000-0003-2237-0128$$aWeiderpass, Elisabete$$b16
000298365 7001_ $$00000-0002-3975-5596$$aEichelmann, Fabian$$b17
000298365 7001_ $$00000-0002-0830-5277$$aSchulze, Matthias B$$b18
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000298365 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aTurzanski-Fortner, Renée$$b20$$udkfz
000298365 7001_ $$00000-0001-6517-1300$$aHeath, Alicia K$$b21
000298365 7001_ $$00000-0002-4533-1722$$aAune, Dagfinn$$b22
000298365 7001_ $$00000-0003-4446-2138$$aHarewood, Rhea$$b23
000298365 7001_ $$00000-0003-0481-2893$$aDahm, Christina C$$b24
000298365 7001_ $$00000-0002-5879-2894$$aLlorente, Adrian$$b25
000298365 7001_ $$00000-0001-5472-6761$$aGunter, Marc J$$b26
000298365 7001_ $$00000-0003-3347-8249$$aMurphy, Neil$$b27
000298365 7001_ $$00000-0003-4311-6890$$aLewis, Sarah J$$b28
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