TY - JOUR
T1 - Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort
AU - Rothwell, Joseph A.
AU - Murphy, Neil
AU - Bešević, Jelena
AU - Kliemann, Nathalie
AU - Jenab, Mazda
AU - Ferrari, Pietro
AU - Achaintre, David
AU - Gicquiau, Audrey
AU - Vozar, Béatrice
AU - Scalbert, Augustin
AU - Huybrechts, Inge
AU - Freisling, Heinz
AU - Prehn, Cornelia
AU - Adamski, Jerzy
AU - Cross, Amanda J.
AU - Pala, Valeria Maria
AU - Boutron-Ruault, Marie Christine
AU - Dahm, Christina C.
AU - Overvad, Kim
AU - Gram, Inger Torhild
AU - Sandanger, Torkjel M.
AU - Skeie, Guri
AU - Jakszyn, Paula
AU - Tsilidis, Kostas K.
AU - Aleksandrova, Krasimira
AU - Schulze, Matthias B.
AU - Hughes, David J.
AU - van Guelpen, Bethany
AU - Bodén, Stina
AU - Sánchez, Maria José
AU - Schmidt, Julie A.
AU - Katzke, Verena
AU - Kühn, Tilman
AU - Colorado-Yohar, Sandra
AU - Tumino, Rosario
AU - Bueno-de-Mesquita, Bas
AU - Vineis, Paolo
AU - Masala, Giovanna
AU - Panico, Salvatore
AU - Eriksen, Anne Kirstine
AU - Tjønneland, Anne
AU - Aune, Dagfinn
AU - Weiderpass, Elisabete
AU - Severi, Gianluca
AU - Chajès, Véronique
AU - Gunter, Marc J.
N1 - Funding Information:
Funding This work was supported by the World Cancer Research Fund grant 2013-1002 and the European Commission grant EU-FP7/BBMRI-LPC - number 313010 (M.J.G.). The coordination of the European Prospective Investigation into Cancer and Nutrition is supported financially by the International Agency for Research on Cancer and Imperial College London . The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer , Institut Gustave-Roussy , Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (France); German Cancer Aid , German Cancer Research Center , Federal Ministry of Education and Research , Deutsche Krebshilfe , and Deutsches Krebsforschungszentrum (Germany) ; Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro Italy and the National Research Council (Italy); Dutch Ministry of Public Health , Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, and Statistics Netherlands (The Netherlands); Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund, PI13/00061 to Granada; PI13/01162 to European Prospective Investigation into Cancer and Nutrition–Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (6236), and Navarra, Instituto de Salud Carlos III Cooperative Research in Health (RD06/0020) (Spain); Swedish Cancer Society , Swedish Research Council , and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to European Prospective Investigation into Cancer and Nutrition–Norfolk, and C570/A16491 and C8221/A19170 to European Prospective Investigation into Cancer and Nutrition–Oxford), and the Medical Research Council (1000143 to European Prospective Investigation into Cancer and Nutrition–Norfolk, and MR/M012190/1 to European Prospective Investigation into Cancer and Nutrition–Oxford) (United Kingdom). For information on how to submit an application for gaining access to European Prospective Investigation into Cancer and Nutrition data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php .
Funding Information:
Funding This work was supported by the World Cancer Research Fund grant 2013-1002 and the European Commission grant EU-FP7/BBMRI-LPC - number 313010 (M.J.G.). The coordination of the European Prospective Investigation into Cancer and Nutrition is supported financially by the International Agency for Research on Cancer and Imperial College London. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, and Institut National de la Santé et de la Recherche Médicale (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research, Deutsche Krebshilfe, and Deutsches Krebsforschungszentrum (Germany); Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro Italy and the National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, and Statistics Netherlands (The Netherlands); Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund, PI13/00061 to Granada; PI13/01162 to European Prospective Investigation into Cancer and Nutrition–Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (6236), and Navarra, Instituto de Salud Carlos III Cooperative Research in Health (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to European Prospective Investigation into Cancer and Nutrition–Norfolk, and C570/A16491 and C8221/A19170 to European Prospective Investigation into Cancer and Nutrition–Oxford), and the Medical Research Council (1000143 to European Prospective Investigation into Cancer and Nutrition–Norfolk, and MR/M012190/1 to European Prospective Investigation into Cancer and Nutrition–Oxford) (United Kingdom). For information on how to submit an application for gaining access to European Prospective Investigation into Cancer and Nutrition data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php.
Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
KW - Colorectal Neoplasm
KW - Risk Factors
KW - Targeted Metabolomics
KW - World Cancer Research Fund/American Institute for Cancer Research Recommendations
UR - http://www.scopus.com/inward/record.url?scp=85109819565&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2020.11.045
DO - 10.1016/j.cgh.2020.11.045
M3 - Article
C2 - 33279777
AN - SCOPUS:85109819565
SN - 1542-3565
VL - 20
SP - e1061-e1082
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 5
ER -
