Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort

Joseph A Rothwell; Neil Murphy; Jelena Bešević; Nathalie Kliemann; Mazda Jenab; Pietro Ferrari; David Achaintre; Audrey Gicquiau; Béatrice Vozar; Augustin Scalbert; Inge Huybrechts; Heinz Freisling; Cornelia Prehn; Jerzy Adamski; Amanda J Cross; Valeria Maria Pala; Marie-Christine Boutron-Ruault; Christina C Dahm; Kim Overvad; Inger Torhild Gram; Torkjel M Sandanger; Guri Skeie; Paula Jakszyn; Kostas K Tsilidis; Krasimira Aleksandrova; Matthias B Schulze; David J Hughes; Bethany van Guelpen; Stina Bodén; Maria-José Sánchez; Julie A Schmidt; Verena Katzke; Tilman Kühn; Sandra Colorado-Yohar; Rosario Tumino; Bas Bueno-de-Mesquita; Paolo Vineis; Giovanna Masala; Salvatore Panico; Anne Kirstine Eriksen; Anne Tjønneland; Dagfinn Aune; Elisabete Weiderpass; Gianluca Severi; Véronique Chajès; Marc J Gunter

doi:10.1016/j.cgh.2020.11.045

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort

Clin Gastroenterol Hepatol. 2022 May;20(5):e1061-e1082. doi: 10.1016/j.cgh.2020.11.045. Epub 2020 Dec 29.

Authors

Joseph A Rothwell¹, Neil Murphy², Jelena Bešević³, Nathalie Kliemann², Mazda Jenab², Pietro Ferrari², David Achaintre², Audrey Gicquiau², Béatrice Vozar², Augustin Scalbert², Inge Huybrechts², Heinz Freisling², Cornelia Prehn³, Jerzy Adamski⁴, Amanda J Cross³, Valeria Maria Pala³, Marie-Christine Boutron-Ruault⁵, Christina C Dahm⁶, Kim Overvad⁶, Inger Torhild Gram⁷, Torkjel M Sandanger⁷, Guri Skeie⁷, Paula Jakszyn⁸, Kostas K Tsilidis⁹, Krasimira Aleksandrova¹⁰, Matthias B Schulze¹¹, David J Hughes¹², Bethany van Guelpen¹³, Stina Bodén¹³, Maria-José Sánchez¹⁴, Julie A Schmidt¹⁵, Verena Katzke¹⁶, Tilman Kühn¹⁶, Sandra Colorado-Yohar¹⁷, Rosario Tumino¹⁸, Bas Bueno-de-Mesquita¹⁹, Paolo Vineis²⁰, Giovanna Masala²¹, Salvatore Panico²², Anne Kirstine Eriksen²³, Anne Tjønneland²³, Dagfinn Aune²⁴, Elisabete Weiderpass², Gianluca Severi⁵, Véronique Chajès², Marc J Gunter²

Affiliations

¹ Centre for Epidemiology and Population Health, U1018, Generations and Health Team, Faculté de Médecine, Université Paris-Saclay, INSERM, Villejuif, France; Gustave Roussy, Villejuif, France; International Agency for Research on Cancer, Lyon, France. Electronic address: joseph.rothwell@inserm.fr.
² International Agency for Research on Cancer, Lyon, France.
³ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
⁴ Research Unit, Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, Neuherberg, Germany; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, Neuherberg, Germany.
⁵ Centre for Epidemiology and Population Health, U1018, Generations and Health Team, Faculté de Médecine, Université Paris-Saclay, INSERM, Villejuif, France; Gustave Roussy, Villejuif, France.
⁶ Department of Public Health, Aarhus University, Aarhus C, Denmark.
⁷ Faculty of Health Sciences, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
⁸ Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Barcelona, Spain; Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain.
⁹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
¹⁰ Nutrition, Immunity and Metabolism Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
¹¹ Institute of Nutritional Science, University of Potsdam, Potsdam, Germany; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
¹² School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.
¹³ Department of Radiation Sciences, Oncology Unit, Umea University, Umea, Sweden.
¹⁴ CIBER Epidemiología y Salud Pública, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
¹⁵ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
¹⁶ Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum, Stiftung des Öffentlichen Rechts, Heidelberg, Germany.
¹⁷ Department of Epidemiology, Murcia Regional Health Council, Instituto Murciano de Investigatión Biomédica (IMIB)-Arrixaca, Murcia, Spain; CIBER Epidemiología y Salud Pública, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.
¹⁸ Cancer Registry and Histopathology Department, Provincial Health Authority, Ragusa, Italy.
¹⁹ Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, BA Bilthoven, The Netherlands.
²⁰ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Italian Institute of Technology, Genova, Italy.
²¹ Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Florence, Italy.
²² Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
²³ Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark.
²⁴ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Nutrition, Bjørknes University College, Oslo, Norway; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.

Abstract

Background & aims: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Methods: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.

Results: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.

Conclusions: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

Keywords: Colorectal Neoplasm; Risk Factors; Targeted Metabolomics; World Cancer Research Fund/American Institute for Cancer Research Recommendations.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Colorectal Neoplasms* / epidemiology
Diet / adverse effects
Fatty Acids
Female
Healthy Lifestyle*
Humans
Male
Prospective Studies
Risk Factors

Substances

Fatty Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding