TY  - JOUR
A1  - Rothwell, Joseph A.
A1  - Murphy, Neil
A1  - Aleksandrova, Krasimira
A1  - Schulze, Matthias B.
A1  - Bešević, Jelena
A1  - Kliemann, Nathalie
A1  - Jenab, Mazda
A1  - Ferrari, Pietro
A1  - Achaintre, David
A1  - Gicquiau, Audrey
A1  - Vozar, Béatrice
A1  - Scalbert, Augustin
A1  - Huybrechts, Inge
A1  - Freisling, Heinz
A1  - Prehn, Cornelia
A1  - Adamski, Jerzy
A1  - Cross, Amanda J.
A1  - Pala, Valeria Maria
A1  - Boutron-Ruault, Marie-Christine
A1  - Dahm, Christina C.
A1  - Overvad, Kim
A1  - Gram, Inger Torhild
A1  - Sandanger, Torkjel M.
A1  - Skeie, Guri
A1  - Jakszyn, Paula
A1  - Tsilidis, Kostas K.
A1  - Hughes, David J.
A1  - van Guelpen, Bethany
A1  - Bodén, Stina
A1  - Sánchez, Maria-José
A1  - Schmidt, Julie A.
A1  - Katzke, Verena
A1  - Kühn, Tilman
A1  - Colorado-Yohar, Sandra
A1  - Tumino, Rosario
A1  - Bueno-de-Mesquita, Bas
A1  - Vineis, Paolo
A1  - Masala, Giovanna
A1  - Panico, Salvatore
A1  - Eriksen, Anne Kirstine
A1  - Tjønneland, Anne
A1  - Aune, Dagfinn
A1  - Weiderpass, Elisabete
A1  - Severi, Gianluca
A1  - Chajès, Véronique
A1  - Gunter, Marc J.
T1  - Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
JF  - Clinical gastroenterology and hepatology
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.
KW  - colorectal neoplasm
KW  - risk factors
KW  - World Cancer Research Fund/American Institute for Cancer Research Recommendations
KW  - targeted metabolomics
Y1  - 2020
U6  - https://doi.org/10.1016/j.cgh.2020.11.045
SN  - 1542-3565
SN  - 1542-7714
VL  - 20
SP  - E1061
EP  - E1082
PB  - Elsevier
CY  - New York, NY
ER  -