Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study

Tilman Kühn, Magdalena Stepien, Marina López-Nogueroles, Antje Damms Machado, Disorn Sookthai, Theron Johnson, Marta Roca, Anika Hüsing, Sandra González Maldonado, Amanda J Cross, Neil Murphy, Heinz Freisling, Sabina Rinaldi, Augustin Scalbert, Veronika Fedirco, Gianluca Severi, Marie-Christine Boutron-Ruault, Francesca Romana Mancini, Solomon A Sowah, Heiner BoeingPaula Jakszyn, Maria-Jose Sánchez, Susana Merino, Sandra Colorado-Yohar, Aurelio Barricarte, Kay Tee Khaw, Julie A Schmidt, Aurora Perez-Cornago, Antonia Trichopoulou, Anna Karakatsani, Paschalis Thriskos, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Bas Bueno-de-Mesquita, Carla H van Gils, Alicia Heath, Marc J Gunter, Elio Riboli, Agustín Lahoz, Mazda Jenab, Rudolf Kaaks

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Abstract

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 pre-diagnostic 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 7 conjugated bile acid metabolites, i.e. primary bile acids glycocholic acid (ORQuartile 4 vs. Quartile 1=2.22,95 % confidence interval[CI]=1.52, 3.26), taurocholic acid (OR = 1.78, 95%CI=1.23, 2.58), glycochenodeoxycholic acid (OR = 1.68, 95%CI=1.13, 2.48), taurochenodeoxycholic acid (OR = 1.62, 95%CI=1.11-2.36), and glycohyocholic acid (OR = 1.65, 95%CI=1.13, 2.40) as well as the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95%CI=1.12, 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI=1.02, 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.

CONCLUSIONS: This prospective study showed that pre-diagnostic 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.

Original languageEnglish
JournalJournal of the National Cancer Institute
Early online date21 Aug 2019
DOIs
Publication statusEarly online date - 21 Aug 2019

Bibliographical note

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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    Kühn, T., Stepien, M., López-Nogueroles, M., Machado, A. D., Sookthai, D., Johnson, T., Roca, M., Hüsing, A., Maldonado, S. G., Cross, A. J., Murphy, N., Freisling, H., Rinaldi, S., Scalbert, A., Fedirco, V., Severi, G., Boutron-Ruault, M-C., Mancini, F. R., Sowah, S. A., ... Kaaks, R. (2019). Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study. Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/djz166