Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-04

AUTHORS

Veronika Fedirko, Hao Quang Tran, Andrew T. Gewirtz, Magdalena Stepien, Antonia Trichopoulou, Krasimira Aleksandrova, Anja Olsen, Anne Tjønneland, Kim Overvad, Franck Carbonnel, Marie-Christine Boutron-Ruault, Gianluca Severi, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Christina Bamia, Pagona Lagiou, Sara Grioni, Salvatore Panico, Domenico Palli, Rosario Tumino, Alessio Naccarati, Petra H. Peeters, H. B. Bueno-de-Mesquita, Elisabete Weiderpass, José María Huerta Castaño, Aurelio Barricarte, María-José Sánchez, Miren Dorronsoro, J. Ramón Quirós, Antonio Agudo, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Kathryn E. Bradbury, Kay-Tee Khaw, Nick Wareham, Konstantinos K. Tsilidis, Dagfinn Aune, Augustin Scalbert, Isabelle Romieu, Elio Riboli, Mazda Jenab

ABSTRACT

BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted. More... »

PAGES

72

Journal

TITLE

BMC Medicine

ISSUE

1

VOLUME

15

Author Affiliations

  • Winship Cancer Institute, Emory University, Atlanta, GA USA
  • Center for Inflammation, Immunity, and Infection Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303 USA
  • Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, University of Athens Medical School, Athens, Greece
  • Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutrition, Immunity and Metabolism Start-up Lab, Nuthetal, Germany
  • Danish Cancer Society Research Center, Copenhagen, Denmark
  • Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
  • Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), University hospitals Paris-Sud, Site de Bicêtre, Paris Sud University, Paris XI, Le Kremlin Bicêtre, Villejuif, France
  • Gustave Roussy, Villejuif, F-94805 France
  • Cancer Council Victoria and University of Melbourne, Melbourne, Australia
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
  • Department of Epidemiology, Harvard School of Public Health, Boston, MA USA
  • Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, 1 20133 Milano, Italy
  • Dipartimento di Medicina Clinica Echirurgia Federico II University, Naples, Italy
  • Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy
  • Cancer Registry and Histopathology Unit, “Civic -M.P. Arezzo” Hospital, ASP, Ragusa, Italy
  • Molecular and Genetic Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino, Italy
  • Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  • Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland
  • CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  • Navarra Institute for Health Research (IdiSNA), Pamplona, Spain
  • Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada, Universidad de Granada, Granada, Spain
  • Basque Regional Health Department, San Sebastian, Spain
  • Public Health Directorate, Asturias, Spain
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
  • Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden
  • Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund, Sweden
  • Department of Surgical and Perioperative Sciences, Kirurgcentrum, Norrlands Universitetssjukhus, Umeå, Sweden
  • Department of Medicine Sections for Hepatology and Gastroenterology, Umeå University Hospital, SE-90185 Umeå, Sweden
  • Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • Clinical Gerontology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK
  • MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12916-017-0830-8

    DOI

    http://dx.doi.org/10.1186/s12916-017-0830-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084251057

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28372583


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