Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

doi:10.1158/1055-9965.EPI-19-0313

. 2019 Sep;28(9):1552-1555.

doi: 10.1158/1055-9965.EPI-19-0313.

Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

Julia Butt^#^{1

2}, Mazda Jenab^#³, Michael Pawlita¹, Kim Overvad⁴, Anne Tjonneland⁵, Anja Olsen⁵, Marie-Christine Boutron-Ruault^{6

7}, Franck Carbonnel^{6

7

8}, Francesca Romana Mancini^{6

7}, Rudolf Kaaks⁹, Tilman Kühn⁹, Heiner Boeing¹⁰, Antonia Trichopoulou^{11

12}, Anna Karakatsani^{11

13}, Domenico Palli¹⁴, Valeria Maria Pala¹⁵, Rosario Tumino¹⁶, Carlotta Sacerdote¹⁷, Salvatore Panico¹⁸, Bas Bueno-de-Mesquita^{19

20

21

22}, Carla H van Gils²³, Roel C H Vermeulen^{23

24}, Elisabete Weiderpass^{25

26

27

28}, José Ramón Quirós²⁹, Eric Jeffrey Duell³⁰, Maria-Jose Sánchez^{31

32}, Miren Dorronsoro³³, José María Huerta^{32

34}, Eva Ardanaz^{32

35

36}, Bethany Van Guelpen³⁷, Sophia Harlid³⁷, Aurora Perez-Cornago³⁸, Marc J Gunter³, Neil Murphy³, Heinz Freisling³, Dagfinn Aune²¹, Tim Waterboer^#¹, David J Hughes^#³⁹

Affiliations

¹ Infection and Cancer Epidemiology, Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Faculty of Biosciences, University of Heidelberg, Germany.
³ Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
⁴ Department of Cardiology and Department of Clinical Epidemiology, Aarhus Hospital, Aalborg, Denmark.
⁵ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁶ CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
⁷ Gustave Roussy, Villejuif, France.
⁸ Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France.
⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁰ Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
¹¹ Hellenic Health Foundation, Athens, Greece.
¹² WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece.
¹³ 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece.
¹⁴ Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
¹⁵ Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine, Fondazione Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
¹⁷ Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
¹⁸ Dipartimento die Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
¹⁹ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
²⁰ Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
²¹ Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
²² Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²³ Julius Center for Health Sciences and Primary Care, Cancer Epidemiology, University Medical Center Utrecht, the Netherlands.
²⁴ Environmental Epidemiology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
²⁵ Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
²⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁷ Genetic Epidemiology Group, Folkhälsan Research Center, and Faculty of Medicine, Helsinki University, Helsinki, Finland.
²⁸ Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
²⁹ EPIC Asturias, Public Health Directorate Asturias, Oviedo, Spain.
³⁰ Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
³¹ Escuela Andaluza de Salud pública, Instituto de Investigacíon ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
³² CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
³³ Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
³⁴ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
³⁵ Navarra Public Health Institute, Pamplona, Spain.
³⁶ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³⁷ Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
³⁸ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
³⁹ Cancer Biology and Therapeutics Group, UCD Conway Institute, University College Dublin, Dublin, Ireland. david.hughes@ucd.ie.

^# Contributed equally.

PMID: 31481495
DOI: 10.1158/1055-9965.EPI-19-0313

Free article

Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

Julia Butt et al. Cancer Epidemiol Biomarkers Prev. 2019 Sep.

Free article

. 2019 Sep;28(9):1552-1555.

doi: 10.1158/1055-9965.EPI-19-0313.

Authors

Affiliations

¹ Infection and Cancer Epidemiology, Division of Molecular Diagnostics of Oncogenic Infections, German Cancer Research Center (DKFZ), Heidelberg, Germany.
² Faculty of Biosciences, University of Heidelberg, Germany.
³ Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
⁴ Department of Cardiology and Department of Clinical Epidemiology, Aarhus Hospital, Aalborg, Denmark.
⁵ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁶ CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
⁷ Gustave Roussy, Villejuif, France.
⁸ Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France.
⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
¹⁰ Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
¹¹ Hellenic Health Foundation, Athens, Greece.
¹² WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece.
¹³ 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece.
¹⁴ Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy.
¹⁵ Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine, Fondazione Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
¹⁷ Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
¹⁸ Dipartimento die Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
¹⁹ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
²⁰ Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
²¹ Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
²² Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
²³ Julius Center for Health Sciences and Primary Care, Cancer Epidemiology, University Medical Center Utrecht, the Netherlands.
²⁴ Environmental Epidemiology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
²⁵ Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
²⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁷ Genetic Epidemiology Group, Folkhälsan Research Center, and Faculty of Medicine, Helsinki University, Helsinki, Finland.
²⁸ Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
²⁹ EPIC Asturias, Public Health Directorate Asturias, Oviedo, Spain.
³⁰ Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
³¹ Escuela Andaluza de Salud pública, Instituto de Investigacíon ibs.Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
³² CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
³³ Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
³⁴ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
³⁵ Navarra Public Health Institute, Pamplona, Spain.
³⁶ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³⁷ Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
³⁸ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
³⁹ Cancer Biology and Therapeutics Group, UCD Conway Institute, University College Dublin, Dublin, Ireland. david.hughes@ucd.ie.

^# Contributed equally.

PMID: 31481495
DOI: 10.1158/1055-9965.EPI-19-0313

Abstract

Background: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.

Methods: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).

Results: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62-1.06).

Conclusions: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.

Impact: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

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Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

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Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer

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