Pre-diagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma.

Fecha de publicación: 15/04/2022 Fecha Ahead of Print: 29/11/2021

Autores de IIS La Fe

Marina López Nogueroles

Autor
Agustín Lahoz Rodríguez

Autor

Participantes ajenos a IIS La Fe

Stepien, Magdalena
Kühn T
Perlemuter, Gabriel
Voican, Cosmin
Ciocan, Dragos
Boutron-Ruault, Marie-Christine
Jansen, Eugene
Viallon, Vivian
Leitzmann, Michael
Tjønneland A
Severi, Gianluca
Mancini, Francesca Romana
Dong, Catherine
Kaaks, Rudolf
Fortner, Renee Turzanski
Bergmann, Manuela M.
Boeing, Heiner
Trichopoulou, Antonia
Karakatsani, Anna
Peppa, Eleni
Palli, Domenico
Krogh, Vittorio
Tumino, Rosario
Sacerdote, Carlotta
Panico, Salvatore
Bueno-de-Mesquita, H. Bas
Skeie, Guri
Merino, Susana
Ros, Raul Zamora
Sanchez, Maria Jose
Amiano, Pilar
Huerta, Jose Ma
Barricarte, Aurelio
Sjöberg K
Ohlsson, Bodil
Nyström H
Werner, Marten
Perez-Cornago, Aurora
Schmidt, Julie A.
Freisling, Heinz
Scalbert, Augustin
Weiderpass, Elisabete
Christakoudi, Sofia
Gunter, Marc J.
Jenab, Mazda

Grupos

Unidad de Biomarcadores y Medicina de Precisión (UBYMP)

Leader

Agustín Lahoz Rodríguez

Abstract

Bile acids (BA) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory, and immune-related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case-control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow-up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/un-conjugated) in pre-diagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (OR(doubling) = 2.30, 95%CI = 1.76-3.00) and choline- and taurine-conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine-conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increased in BA concentration is accompanied by a shift in BA profile towards higher proportions of taurine-conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction. This article is protected by copyright. All rights reserved.

Datos de la publicación

ISSN/ISSNe:: 0020-7136, 1097-0215
Tipo:: Article
Páginas:: 1255-1268
DOI:: 10.1002/ijc.33885
Factor de Impacto:: 2,056 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Stepien, Magdalena:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Lopez-Nogueroles, Marina:: Instituto de Investigación. Analytical Unit, Health Research Institute Hospital La Fe, Valencia, Spain
Lahoz, Agustin:: Instituto de Investigación. Analytical Unit, Health Research Institute Hospital La Fe, Valencia, Spain
Kühn T:: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Perlemuter, Gabriel:: INSERM U996, Intestinal Microbiota, Macrophages and Liver Inflammation, DHU Hepatinov, Labex LERMIT, Clamart, France

Faculté de Médecine Paris-Sud, Univ Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France

Service d'hépato-gastroentérologie, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France
Voican, Cosmin:: INSERM U996, Intestinal Microbiota, Macrophages and Liver Inflammation, DHU Hepatinov, Labex LERMIT, Clamart, France

Faculté de Médecine Paris-Sud, Univ Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France

Service d'hépato-gastroentérologie, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France
Ciocan, Dragos:: INSERM U996, Intestinal Microbiota, Macrophages and Liver Inflammation, DHU Hepatinov, Labex LERMIT, Clamart, France

Faculté de Médecine Paris-Sud, Univ Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France

Service d'hépato-gastroentérologie, Hôpital Antoine-Béclère, Hôpitaux Universitaires Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France
Boutron-Ruault, Marie-Christine:: CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France

Gustave Roussy, Villejuif, France
Viallon, Vivian:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Leitzmann, Michael:: Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
Tjønneland A:: Diet, Genes and Environment Unit, Danish Cancer Society Research Center, Copenhagen, Denmark
Severi, Gianluca:: CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France

Gustave Roussy, Villejuif, France
Mancini, Francesca Romana:: CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France

Gustave Roussy, Villejuif, France
Dong, Catherine:: CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France

Gustave Roussy, Villejuif, France

Hôpital de Bicêtre, department of Gastroenterology, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
Kaaks, Rudolf:: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Fortner, Renee Turzanski:: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Bergmann, Manuela M.:: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
Boeing, Heiner:: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
Trichopoulou, Antonia:: Hellenic Health Foundation, Athens, Greece
Karakatsani, Anna:: Hellenic Health Foundation, Athens, Greece

2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece
Peppa, Eleni:: Hellenic Health Foundation, Athens, Greece
Palli, Domenico:: Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
Krogh, Vittorio:: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Italy
Tumino, Rosario:: Cancer Registry and Histopathology Department, "M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy
Sacerdote, Carlotta:: Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy
Panico, Salvatore:: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
Bueno-de-Mesquita, H. Bas:: Former Visiting professor, Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London, UK

Former Academic Icon / visiting professor, Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, 50603, Kuala Lumpur, Malaysia
Skeie, Guri:: Department of Community Medicine, UIT - the Arctic University of Norway, Tromsø, Norway
Merino, Susana:: Public Health Directorate, Asturias, Spain
Ros, Raul Zamora:: Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain
Sanchez, Maria Jose:: Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA, Universidad de Granada, Granada, Spain

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Amiano, Pilar:: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain
Huerta, Jose Ma:: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
Barricarte, Aurelio:: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Navarra Public Health Institute, Pamplona, Spain

Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
Sjöberg K:: Lund University, Skåne University Hospital, Department of Gastroenterology and Nutrition, Malmö, Sweden
Ohlsson, Bodil:: Lund University, Skåne University Hospital, Department of Internal Medicine, Malmö, Sweden
Nyström H:: Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden
Werner, Marten:: Department of Public Health and Clinical Medicine, Umeå University, Sweden
Perez-Cornago, Aurora:: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
Schmidt, Julie A.:: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
Freisling, Heinz:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Scalbert, Augustin:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Weiderpass, Elisabete:: Office of the Director, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Christakoudi, Sofia:: Department of Epidemiology and Biostatistics, Imperial College London, London, UK

MRC Centre for Transplantation, King's College London, Great Maze Pond, London, UK
Gunter, Marc J.:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
Jenab, Mazda:: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France