Abstract

Antibodies to Streptococcus gallolyticus subspecies gallolyticus (SGG) have been associated with colorectal cancer (CRC). Because SGG may correlate with impaired gut epithelia, we assessed the association of antibodies to bacterial flagellin C (FliC), a measure potentially related to this impairment, with CRC and the CRC-specific interaction with antibodies to SGG proteins. Antibodies to FliC and SGG pilus proteins Gallo2178 and Gallo2179 were measured in two independent studies, a combined study from Nijmegen and Detroit (93 CRC cases, 74 controls) and a replication data set including 576 cases and 576 controls from the Spanish multicenter multicase-control study (MCC-Spain). Logistic regression was applied to assess whether antibodies to FliC were associated with CRC and modified the association of antibodies to SGG proteins with CRC. Antibodies to FliC were associated with those to SGG Gallo2178 among CRC cases, resulting in an interaction in the association of antibodies to Gallo2178 with CRC (p = 0.007). This association was only present among individuals with high antibody responses to FliC (OR: 2.42, 95% CI: 1.45–4.06). In conclusion, our findings suggest that colorectal tumorigenesis could be accompanied by an impaired integrity of the epithelium that could result in associated increased antibody responses to bacterial proteins.

Details

Title
Antibody responses to flagellin C and Streptococcus gallolyticus pilus proteins in colorectal cancer
Author
Butt, Julia 1 ; Nerea Fernández de Larrea 2 ; Tjalsma, Harold 3 ; Roelofs, Rian 4 ; Kato, Ikuko 5 ; Martín, Vicente 6   VIAFID ORCID Logo  ; Pérez-Gómez, Beatriz 7   VIAFID ORCID Logo  ; Moreno, Victor 8   VIAFID ORCID Logo  ; Dierssen-Sotos, Trinidad 9 ; Castilla, Jesús 10   VIAFID ORCID Logo  ; Fernández-Tardón, Guillermo 11 ; Amiano, Pilar 12 ; Salas, Dolores 13 ; Alguacil, Juan 14 ; José Juan Jiménez-Moleón 15   VIAFID ORCID Logo  ; Huerta, José María 16 ; de Sanjosé, Silvia 17 ; Rosa del Campo 18   VIAFID ORCID Logo  ; Kogevinas, Manolis 19 ; Pollán, Marina 2 ; Pawlita, Michael 20 ; Waterboer, Tim 20 ; Boleij, Annemarie 21   VIAFID ORCID Logo  ; Aragonés, Nuria 22 

1  Infection and Cancer Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany 
2  Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain 
3  Independent researcher. Experimental work conducted at the Department of Laboratory Medicine, Radboud University Medical Centre (RadboudUMC), Nijmegen, The Netherlands 
4  Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud university medical centre (Radboudumc), Nijmegen, The Netherlands 
5  Departments of Oncology and Pathology, Wayne State University, Detroit, Michigan, USA 
6  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; The Research Group in Gene Environment and Health Interactions, University of León, León, Spain 
7  Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Cardiovascular and Metabolic Diseases Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain 
8  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Hospitalet de Llobregat, Barcelona, Spain; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain 
9  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; University of Cantabria – IDIVAL, Santander, Spain 
10  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Public Health Institute of Navarra, IdiSNA- Navarra Institute for Health Research, Pamplona, Spain 
11  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; IUOPA, University of Oviedo, Oviedo, Spain 
12  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Public Health Division of Gipuzkoa, BioDonostia Research institute, San Sebastian, Spain 
13  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Cancer and Public Health Area, FISABIO – Public Health, Valencia, Spain; General Directorate Public Health, Valencian Community, Valencia, Spain 
14  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Natural Resources, Health and Environment Research Center (RENSMA), University of Huelva, Huelva, Spain 
15  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Granada Health Research Institute (ibs.GRANADA), Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain 
16  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain 
17  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain; PATH, Reproductive Health, Seattle, USA 
18  Department of Microbiology, Ramón y Cajal Health Research Institute (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain 
19  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; ISGlobal, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Pompeu Fabra University (UPF), Barcelona, Spain 
20  Infection and Cancer Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany 
21  Department of Pathology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud university medical centre (Radboudumc), Nijmegen, The Netherlands 
22  Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Epidemiology Section, Public Health Division, Department of Health of Madrid, Madrid, Spain 
Pages
1-7
Publication year
2019
Publication date
Jul 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-47347-6
ProQuest document ID
2264592160
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.