Association of pre-diagnostic antibody responses to escherichia coli and bacteroides fragilis toxin proteins with colorectal cancer in a European cohort

Butt, Julia and Jenab, Mazda and Werner, Jill and Fedirko, Veronika and Weiderpass, Elisabete and Dahm, Christina C. and Tjonneland, Anne and Olsen, Anja and Boutron-Ruault, Marie-Christine and Rothwell, Joseph A. and Severi, Gianluca and Kaaks, Rudolf and Turzanski-Fortner, Renee and Aleksandrova, Krasimira and Schulze, Matthias and Palli, Domenico and Pala, Valeria and Panico, Salvatore and Tumino, Rosario and Sacerdote, Carlotta and Bueno-de-Mesquita, Bas and Van Gils, Carla H. and Gram, Inger Torhild and Lukic, Marko and Sala, Nuria and Sanchez Perez, Maria Jose and Ardanaz, Eva and Chirlaque, Maria-Dolores and Palmquist, Richard and Lowenmark, Thyra and Travis, Ruth C. and Heath, Alicia and Cross, Amanda J. and Freisling, Heinz and Zouiouich, Semi and Aglago, Elom and Waterboer, Tim and Hughes, David J. (2021) Association of pre-diagnostic antibody responses to escherichia coli and bacteroides fragilis toxin proteins with colorectal cancer in a European cohort. Gut Microbes, 13 (1). ISSN 1949-0976, DOI

Full text not available from this repository.


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) (p(heterogeneity) = 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.

Item Type: Article
Funders: European Commission European Commission Joint Research, International Agency for Research on Cancer, Danish Cancer Society, Ligue nationale contre le cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Regione Sicilia, Fondazione AIRC per la ricerca sul cancro, Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF), Netherlands Government, Nordic Centre of Excellence programme on Food, Nutrition and Health, Instituto de Salud Carlos III[PI13/00061], Instituto de Salud Carlos III[PI13/01162], Catalan Institute of Oncology (Barcelona), Spain, Swedish Cancer Society, Swedish Scientific Council, County Councils of Skane, Vasterbotten (Sweden), Cancer Research UK[C864/A14136], Cancer Research UK[C8221/A19170], Cancer Research UK[C570/A16491], Cancer Research UK[C8221/A290170], UK Research & Innovation (UKRI) Medical Research Council UK (MRC) European Commission[MR/N003284/1], European Cooperation in Science and Technology (COST)[CA17118]
Uncontrolled Keywords: Colorectal cancer;Escherichia coli;Bacteroides fragilis;Serology;Prospective
Subjects: R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RD Surgery
Depositing User: Ms Zaharah Ramly
Date Deposited: 23 Aug 2022 06:36
Last Modified: 23 Aug 2022 06:36

Actions (login required)

View Item View Item