Association of pre-diagnostic antibody responses to escherichia coli and bacteroides fragilis toxin proteins with colorectal cancer in a European cohort
Document Type
Article
Publication Date
1-1-2021
Abstract
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.
Keywords
Colorectal cancer, Escherichia coli, Bacteroides fragilis, Serology, Prospective
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]
Publication Title
Gut Microbes
Volume
13
Issue
1
Publisher
Taylor & Francis
Publisher Location
530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA