Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort

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  • Julia Butt, German Cancer Research Center (DKFZ)
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  • Mazda Jenab, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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  • Jill Werner, German Cancer Research Center (DKFZ)
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  • Veronika Fedirko, Aarhus Universitet
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  • Elisabete Weiderpass, Emory University
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  • Christina C Dahm
  • Anne Tjønneland, CESP, Danish Cancer Society Research Center
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  • Anja Olsen
  • Marie-Christine Boutron-Ruault, Paris-Saclay University
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  • Joseph A Rothwell, Paris-Saclay University
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  • Gianluca Severi, Paris-Saclay University, University of Florence
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  • Rudolf Kaaks, German Cancer Research Center (DKFZ)
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  • Renée Turzanski-Fortner, German Cancer Research Center (DKFZ)
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  • Krasimira Aleksandrova, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany.
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  • Matthias Schulze, German Institute of Human Nutrition, University of Potsdam
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  • Domenico Palli, Prevention and Clinical Network - ISPRO
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  • Valeria Pala, Epidemiology and Prevention Unit, Milan, Italy.
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  • Salvatore Panico, Federico II University, Naples, Italy.
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  • Rosario Tumino, Cancer Registry and Histopathology Department , Provincial Health Authority (ASP), Ragusa, Italy.
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  • Carlotta Sacerdote, Città della Salute e della Scienza Hospital
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  • Bas Bueno-de-Mesquita, National Institute for Public Health and the Environment (RIVM), Bilthoven, University Medical Centre Utrecht, Imperial College London, University of Malaya
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  • Carla H Van Gils, University Medical Centre Utrecht
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  • Inger Torhild Gram, University of Tromsø, Tromsø
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  • Marko Lukic, UiT The Arctic University of Norway
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  • Núria Sala, Catalan Institute of Oncology-ICO
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  • María José Sánchez Pérez, Escuela Andaluza de Salud Pública (EASP), Granada, Instituto de Investigación Biosanitaria (ibs.GRANADA), Consorcio Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Madrid, Spain., University of Granada
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  • Eva Ardanaz, Navarra Public Health Institute, IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
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  • María-Dolores Chirlaque, University of Murcia, CIBER Epidemiology and Public Health (CIBERESP), Madrid
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  • Richard Palmquist, Umeå University
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  • Thyra Löwenmark, Umeå University
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  • Ruth C Travis, University of Oxford
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  • Alicia Heath, Imperial College, London
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  • Amanda J Cross, Imperial College London, University College Dublin
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  • Heinz Freisling, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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  • Semi Zouiouich, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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  • Elom Aglago, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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  • Tim Waterboer, German Cancer Research Center (DKFZ)
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  • David J Hughes, International Agency for Research on Cancer (IARC-WHO), Lyon, France.

Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.

OriginalsprogEngelsk
TidsskriftGut Microbes
Vol/bind13
Nummer1
Sider (fra-til)1-14
Antal sider14
ISSN1949-0976
DOI
StatusUdgivet - 2021

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