Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship

Nikos Papadimitriou ¹, Nabila Kazmi ^2,3, Konstantinos K Tsilidis ^4,5

¹Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
²MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
³Population Health Sciences, The Medical School, University of Bristol, Bristol, United Kingdom.
⁴Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
⁵Cancer Epidemiology and Prevention Research Unit, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
⁶Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
⁷Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
⁸Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.
⁹Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Cinical Network (ISPRO), Florence, Italy.
¹⁰Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C-BEPH), University of Turin, Turin, Italy.
¹¹Escuela Andaluza de Salud Pública (EASP), Granada, Spain.
¹²Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.
¹³Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁴Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain.
¹⁵Navarre Institute for Health Research (IdiSNA), Pamplona, Spain.
¹⁶Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
¹⁷Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
¹⁸Unit of Medical Statistics, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy.
¹⁹Department of Statistics, Computer Science, Applications "G. Parenti", University of Florence, Florence, Italy.
²⁰Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, France.
²¹Université Paris Cité, CNRS, MAP5, Paris, France.
²²International Agency for Research on Cancer, Lyon, France.
²³Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
²⁴German Center for Diabetes Research (DZD), Neuherberg, Germany.
²⁵Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
²⁶Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁷Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
²⁸Department of Nutrition, Oslo New University College, Oslo, Norway.
²⁹Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
³⁰Department of Public Health, Aarhus University, Aarhus Centrum, Denmark.
³¹Subdirection of Public Health of Guipuzcoa, San Sebastián, Spain.

⁰Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology +

|

January 30, 2025

View abstract on PubMed

Summary

Higher physical activity (PA) is linked to lower colorectal cancer risk. The metabolite phosphatidylcholine ae C34:3 (PC ae C34:3) partially explains this association, offering insights into cancer prevention.

Area Of Science

Metabolomics
Cancer Epidemiology
Physical Activity Research

Background

Growing evidence links higher physical activity (PA) to reduced colorectal cancer (CRC) risk.
The specific biological pathways, particularly the role of circulating metabolites, mediating this relationship are not fully understood.

Purpose Of The Study

To investigate the mediating role of the metabolome in the association between physical activity and colorectal cancer risk.
To identify specific metabolites that may explain how physical activity influences CRC risk.

Main Methods

Utilized targeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort.
Employed mediation analyses within a nested case-control study (1,585 cases, 1,585 controls) to assess metabolite mediation of the PA-CRC association.

Main Results

Physical activity was inversely associated with colorectal cancer risk (OR 0.90).
PA levels correlated with 24 circulating metabolites, notably phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and lysophosphatidylcholine acyl C18:2.
PC ae C34:3 partially mediated the PA-CRC association, accounting for 7.4% of the effect.

Conclusions

The metabolite PC ae C34:3 partially mediates the inverse association between physical activity and colorectal cancer.
Further research with enhanced PA assessment and broader metabolomic profiling is warranted to fully elucidate these mechanisms.

Related Concept Videos

Cancer Prevention

Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...