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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- 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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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Gut Microbes |
| Vol/bind | 13 |
| Udgave nummer | 1 |
| Antal sider | 16 |
| ISSN | 1949-0976 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l?Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); the Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona), Spain; Swedish Cancer Society, Swedish Scientific Council, and County Councils of Sk?ne and V?sterbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A19170, C570/A16491 and C8221/A290170 to EPIC-Oxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford (UK). The funding sources had no influence on the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.Support for this study was also provided by the COST Action CA17118 supported by COST (European Cooperation in Science and Technology, www.cost.eu) to DJH. We would like to thank the 1) Direcci?n General de Salud P?blica, Consejer?a de Sanidad del Principado de Asturias, Oviedo, Spain, and 2) Subdirecci?n de Salud P?blica de Gipuzkoa, Instituto de Investigaci?n BIODONOSTIA, Gobierno Vasco, CIBER de Epidemiolog?a y Salud P?blicam, San Sebastian, Spain for their contribution and ongoing support to the EPIC Study. 2) The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
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