American Association for Cancer Research (AACR)
Cancer Epidemiology Biomarkers and Prevention
,  volume 34 ,  issue 4 ,  pages OF1-OF10

Identifying metabolomic mediators of the physical activity and colorectal cancer relationship

Nikos Papadimitriou 1, 2
, 
Nabila Kazmi 3, 4, 5
, 
Konstantinos Tsilidis 6, 7, 8
, 
Rebecca C Richmond 4, 5, 9
, 
Brigid M. Lynch 10, 11, 12, 13
, 
Benedetta Bendinelli 14, 15
, 
Fulvio Ricceri 16, 17
, 
Maria José Sánchez 18, 19, 20, 21
, 
Camino Trobajo Sanmartín 21, 22, 23, 24
, 
P Jakszyn 25, 26, 27
, 
VITTORIO SIMEON 28, 29
, 
Gianluca Severi 30, 31, 32
, 
Vittorio Perduca 32, 33, 34
, 
Thérèse Truong 32, 35
, 
Pietro Ferrari 1, 2
, 
Keski-Rahkonen P 1, 2
, 
Annette J. Dobson 1, 36
, 
Fabian Eichelmann 37, 38, 39
, 
Matthias Schulze 37, 38, 40
, 
Verena Katzke 41, 42
, 
RENÉE TURZANSKI FORTNER 42, 43, 44
, 
Alicia K. Heath 8, 45
, 
Dagfinn Aune 8, 44, 45, 46
, 
Rhea Harewood 45, 47
, 
Christina C. Dahm 48, 49
, 
A. H. Aginagalde Llorente 50, 51
, 
Marc J Gunter 2, 8, 52
, 
Neil Murphy 1, 2
, 
Sarah J. Lewis 3, 4, 5
1
 
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6Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia. | 
12
 
13
 
14
 
Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy | 
15
 
9Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Cinical Network (ISPRO), Florence, Italy. | 
16
 
17
 
18
 
19
 
20
 
12Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. | 
21
 
22
 
23
 
14Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain. | 
24
 
15Navarre Institute for Health Research (IdiSNA), Pamplona, Spain. | 
25
 
26
 
27
 
28
 
29
 
18Unit of Medical Statistics, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy. | 
30
 
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24German Center for Diabetes Research (DZD), Neuherberg, Germany. | 
40
 
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46
 
28Department of Nutrition, Oslo New University College, Oslo, Norway. | 
47
 
48
 
49
 
50
 
Subdirection of Public Health of Guipuzcoa, Spain | 
51
 
31Subdirection of Public Health of Guipuzcoa, San Sebastián, Spain. | 
52
 
Publication type: Journal Article
Publication date: 2025-01-30
American Association for Cancer Research (AACR)
scimago Q1
wos Q1
SJR: 1.939
CiteScore: 6.4
Impact factor: 3.4
ISSN: 10559965, 15387755
Abstract
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.

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GOST Copy
Papadimitriou N. et al. Identifying metabolomic mediators of the physical activity and colorectal cancer relationship // Cancer Epidemiology Biomarkers and Prevention. 2025. Vol. 34. No. 4. p. OF1-OF10.
GOST all authors (up to 50) Copy
Papadimitriou N. et al. Identifying metabolomic mediators of the physical activity and colorectal cancer relationship // Cancer Epidemiology Biomarkers and Prevention. 2025. Vol. 34. No. 4. p. OF1-OF10.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1158/1055-9965.epi-24-1390
UR - https://aacrjournals.org/cebp/article/doi/10.1158/1055-9965.EPI-24-1390/751360/Identifying-metabolomic-mediators-of-the-physical
TI - Identifying metabolomic mediators of the physical activity and colorectal cancer relationship
T2 - Cancer Epidemiology Biomarkers and Prevention
AU - Papadimitriou, Nikos
AU - Kazmi, Nabila
AU - Tsilidis, Konstantinos
AU - Richmond, Rebecca C
AU - Lynch, Brigid M.
AU - Bendinelli, Benedetta
AU - Ricceri, Fulvio
AU - Sánchez, Maria José
AU - Trobajo Sanmartín, Camino
AU - Jakszyn, P
AU - SIMEON, VITTORIO
AU - Severi, Gianluca
AU - Perduca, Vittorio
AU - Truong, Thérèse
AU - Ferrari, Pietro
AU - P, Keski-Rahkonen
AU - Dobson, Annette J.
AU - Eichelmann, Fabian
AU - Schulze, Matthias
AU - Katzke, Verena
AU - FORTNER, RENÉE TURZANSKI
AU - Heath, Alicia K.
AU - Aune, Dagfinn
AU - Harewood, Rhea
AU - Dahm, Christina C.
AU - Aginagalde Llorente, A. H.
AU - Gunter, Marc J
AU - Murphy, Neil
AU - Lewis, Sarah J.
PY - 2025
DA - 2025/01/30
PB - American Association for Cancer Research (AACR)
SP - OF1-OF10
IS - 4
VL - 34
SN - 1055-9965
SN - 1538-7755
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Papadimitriou,
author = {Nikos Papadimitriou and Nabila Kazmi and Konstantinos Tsilidis and Rebecca C Richmond and Brigid M. Lynch and Benedetta Bendinelli and Fulvio Ricceri and Maria José Sánchez and Camino Trobajo Sanmartín and P Jakszyn and VITTORIO SIMEON and Gianluca Severi and Vittorio Perduca and Thérèse Truong and Pietro Ferrari and Keski-Rahkonen P and Annette J. Dobson and Fabian Eichelmann and Matthias Schulze and Verena Katzke and RENÉE TURZANSKI FORTNER and Alicia K. Heath and Dagfinn Aune and Rhea Harewood and Christina C. Dahm and A. H. Aginagalde Llorente and Marc J Gunter and Neil Murphy and Sarah J. Lewis and others},
title = {Identifying metabolomic mediators of the physical activity and colorectal cancer relationship},
journal = {Cancer Epidemiology Biomarkers and Prevention},
year = {2025},
volume = {34},
publisher = {American Association for Cancer Research (AACR)},
month = {jan},
url = {https://aacrjournals.org/cebp/article/doi/10.1158/1055-9965.EPI-24-1390/751360/Identifying-metabolomic-mediators-of-the-physical},
number = {4},
pages = {OF1--OF10},
doi = {10.1158/1055-9965.epi-24-1390}
}
MLA
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MLA Copy
Papadimitriou, Nikos, et al. “Identifying metabolomic mediators of the physical activity and colorectal cancer relationship.” Cancer Epidemiology Biomarkers and Prevention, vol. 34, no. 4, Jan. 2025, pp. OF1-OF10. https://aacrjournals.org/cebp/article/doi/10.1158/1055-9965.EPI-24-1390/751360/Identifying-metabolomic-mediators-of-the-physical.