Tilman Kühn1, Magdalena Stepien2, Marina López-Nogueroles3, Antje Damms-Machado1, Disorn Sookthai1, Theron Johnson1, Marta Roca3, Anika Hüsing1, Sandra González Maldonado1, Amanda J Cross4,5, Neil Murphy2, Heinz Freisling6, Sabina Rinaldi7, Augustin Scalbert7, Veronika Fedirko8, Gianluca Severi9,10, Marie-Christine Boutron-Ruault9,10, Francesca Romana Mancini9,10, Solomon A Sowah1, Heiner Boeing11, Paula Jakszyn12,13, Maria J Sánchez14,15, Susana Merino16, Sandra Colorado-Yohar15,17,18, Aurelio Barricarte15,19,20, Kay Tee Khaw21, Julie A Schmidt5, Aurora Perez-Cornago5, Antonia Trichopoulou22, Anna Karakatsani22,23, Paschalis Thriskos22, Domenico Palli24, Claudia Agnoli25, Rosario Tumino26, Carlotta Sacerdote27, Salvatore Panico28, Bas Bueno-de-Mesquita4,29,30,31, Carla H van Gils32, Alicia K Heath4, Marc J Gunter2, Elio Riboli4, Agustín Lahoz3, Mazda Jenab2, Rudolf Kaaks1. 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. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 6. Nutritional Methodology and Biostatistics Group. 7. Biomarkers Group. 8. Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta. 9. CESP, Fac. de médecine-Univ. Paris-Sud, Fac. de médecine-UVSQ, INSERM, Université Paris-Saclay, Villejuif. 10. Gustave Roussy, Villejuif, France. 11. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 12. Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, L'Hospitallet de Llobregat, Barcelona, Spain. 13. Facultat de Ciències de la Salut Blanquerna, Universitat Ramón Llull, Barcelona, Spain. 14. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. 15. CIBER de Epidemiología y Salud Pública, Madrid, Spain. 16. Public Health Directorate, Asturias, Spain. 17. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. 18. Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. 19. Navarra Public Health Institute, Pamplona, Spain. 20. Navarra Institute for Health Research Pamplona, Spain. 21. University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, UK. 22. Hellenic Health Foundation, Athens, Greece. 23. 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Haidari, Greece. 24. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy. 25. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 26. Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP, Ragusa, Italy. 27. Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention, Turin, Italy. 28. Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy. 29. Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, the Netherlands. 30. Department of Gastroenterology and Hepatology. 31. University Medical Centre, Utrecht, the Netherlands; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 32. Julius Centre for Health Sciences and Primary Care.
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.
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.
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