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Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study

Kühn T 1 , Stepien M 2 , López-Nogueroles M 3 , Damms-Machado A 1 , Sookthai D 1 , Johnson T 1 Show all authors , Roca M 3 , Hüsing A 1 , Maldonado SG 1 , Cross AJ 4 , Murphy N 2 , Freisling H 5 , Rinaldi S 6 , Scalbert A 6 , Fedirko V 7 , Severi G 8 , Boutron-Ruault MC 8 , Mancini FR 8 , Sowah SA 1 , Boeing H 9 , Jakszyn P 10 , Sánchez MJ 11 , Merino S 12 , Colorado-Yohar S 13 , Barricarte A 13 , Khaw KT 14 , Schmidt JA 15 , Perez-Cornago A 15 , Trichopoulou A 16 , Karakatsani A 16 , Thriskos P 16 , Palli D 17 , Agnoli C 18 , Tumino R 19 , Sacerdote C 20 , Panico S 21 , Bueno-de-Mesquita B 4 , van Gils CH 22 , Heath AK 4 , Gunter MJ 2 , Riboli E 4 , Lahoz A 3 , Jenab M 2 , Kaaks R 1

Affiliations 

  • 1 German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
  • 2 International Agency for Research on Cancer, Nutritional Epidemiology Group
  • 3 Section of Nutrition and Metabolism, Lyon, France; Health Research Institute Hospital La Fe, Analytical Unit, Biomarkers and Precision Medicine Unit Valencia, Spain
  • 4 School of Public Health, Imperial College London, St Mary's Campus, London, UK
  • 5 Nutritional Methodology and Biostatistics Group
  • 6 Biomarkers Group
  • 7 Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta
  • 8 CESP, Fac. de médecine-Univ. Paris-Sud, Fac. de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif
  • 9 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  • 10 Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, L'Hospitallet de Llobregat, Barcelona, Spain
  • 11 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain
  • 12 Public Health Directorate, Asturias, Spain
  • 13 CIBER de Epidemiología y Salud Pública, Madrid, Spain
  • 14 University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK
  • 15 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 16 Hellenic Health Foundation, Athens, Greece
  • 17 Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy
  • 18 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 19 Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP, Ragusa, Italy
  • 20 Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention, Turin, Italy
  • 21 Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy
  • 22 Julius Centre for Health Sciences and Primary Care
J Natl Cancer Inst, 2020 May 01;112(5):516-524.
PMID: 31435679 DOI: 10.1093/jnci/djz166

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 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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