TY - JOUR
T1 - Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk
T2 - A Prospective Study
AU - Kühn, Tilman
AU - Stepien, Magdalena
AU - López-Nogueroles, Marina
AU - Damms-Machado, Antje
AU - Sookthai, Disorn
AU - Johnson, Theron
AU - Roca, Marta
AU - Hüsing, Anika
AU - Maldonado, Sandra González
AU - Cross, Amanda J.
AU - Murphy, Neil
AU - Freisling, Heinz
AU - Rinaldi, Sabina
AU - Scalbert, Augustin
AU - Fedirko, Veronika
AU - Severi, Gianluca
AU - Boutron-Ruault, Marie Christine
AU - Mancini, Francesca Romana
AU - Sowah, Solomon A.
AU - Boeing, Heiner
AU - Jakszyn, Paula
AU - Sánchez, Maria J.
AU - Merino, Susana
AU - Colorado-Yohar, Sandra
AU - Barricarte, Aurelio
AU - Khaw, Kay Tee
AU - Schmidt, Julie A.
AU - Perez-Cornago, Aurora
AU - Trichopoulou, Antonia
AU - Karakatsani, Anna
AU - Thriskos, Paschalis
AU - Palli, Domenico
AU - Agnoli, Claudia
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Panico, Salvatore
AU - Bueno-De-Mesquita, Bas
AU - Van Gils, Carla H.
AU - Heath, Alicia K.
AU - Gunter, Marc J.
AU - Riboli, Elio
AU - Lahoz, Agustín
AU - Jenab, Mazda
AU - Kaaks, Rudolf
N1 - Funding Information:
project Aging and Metabolic Programming (AMPro; DKFZ). The present study was further cofinanced by the European Union through the Operational Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014– 2020 (Hospital La Fe) and by the European Regional Development Fund (FEDER) Institute of Health Carlos III of the Spanish Ministry of Economy and Competitiveness (PI17/01282).
Funding Information:
The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the IARC. The national cohorts are supported by the following funders: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), France; German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Germany; the Hellenic Health Foundation, Greece; Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council, Italy; Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, the Netherlands; Health Research Fund (FIS, PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, PI13/02633 to EPIC-Navarra), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, ISCIII RETIC (RD06/0020), Spain; Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford), United Kingdom.
Funding Information:
Bile acid measurements in the present study were funded by Helmholtz Association of German Research Centers via the
Publisher Copyright:
© 2020 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.
AB - Background: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Methods: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Results: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. Conclusions: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.
UR - http://www.scopus.com/inward/record.url?scp=85084027516&partnerID=8YFLogxK
U2 - 10.1093/jnci/djz166
DO - 10.1093/jnci/djz166
M3 - Article
C2 - 31435679
AN - SCOPUS:85084027516
SN - 0027-8874
VL - 112
SP - 516
EP - 524
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 5
ER -
