Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
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Abstract
BACKGROUND: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. METHODS: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. RESULTS: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10-2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47-1.02; Ptrend, 0.18). CONCLUSION: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. IMPACT: Further studies are warranted to better clarify these preliminary observations.
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A large prospective study of mostly Caucasian persons associated higher lipopolysaccharide levels with increased colorectal cancer risk in men.
“A large prospective study of mostly Caucasian persons associated higher levels of LPS with increased risk of CRC in men,107”
From Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer (2020) · cites this paper as [107]
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- Authors
- Kong, S. Y., Tran, H. Q., Gewirtz, A. T., McKeown-Eyssen, G., Fedirko, V., Romieu, I., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Bastide, N., Affret, A., Kühn, T., Kaaks, R., Boeing, H., Aleksandrova, K., Trichopoulou, A., Kritikou, M., Vasilopoulou, E., Palli, D., Krogh, V., Mattiello, A., Tumino, R., Naccarati, A., Bueno-de-Mesquita, H. B., Peeters, P. H., Weiderpass, E., Quirós, J. R., Sala, N., Sánchez, M.-J., Castaño, J. M. H., Barricarte, A., Dorronsoro, M., Werner, M., Wareham, N. J., Khaw, K.-T., Bradbury, K. E., Freisling, H., Stavropoulou, F., Ferrari, P., Gunter, M. J., Cross, A. J., Riboli, E., Bruce, W. R., & Jenab, M.
- Affiliations
- Centre international de recherche sur le cancer (FR)
- Georgia State University (US)
- 3Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
- Emory University (US)
- Danish Cancer Society (DK)
- Aarhus University (DK)
- 7INSERM, CESP Centre for Research in Epidemiology and Population Health, Lifestyle, Genes, and Health: Integrative Trans-Generational Epidemiology, Villejuif, France.
- Université Paris-Sud (FR)
- 10Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- German Cancer Research Center (DE)
- German Institute of Human Nutrition (DE)
- National and Kapodistrian University of Athens (GR)
- Hellenic Health Foundation (GR)
- 14Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy.
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Federico II University Hospital (IT)
- 17Cancer Registry and Histopathology Unit, “Civic – MP Arezzo” Hospital, Ragusa, Italy.
- Italian institute for Genomic Medicine (IT)
- University Medical Center Utrecht (NL)
- Karolinska Institutet (SE)
- 29Public Health Directorate, Asturias, Spain.
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Universidad de Granada (ES)
- 32CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
- Instituto de Salud Pública de Navarra (ES)
- Biogipuzkoa Health Research Institute (ES)
- Umeå University (SE)
- Addenbrooke's Hospital (GB)
- University of Cambridge (GB)
- University of Oxford (GB)
- Imperial College London (GB)
- 21Department of Epidemiology and Biostatistics, School of Public Health, Imperil College London, London, United Kingdom.
- University of Toronto (CA)
- Corresponding author
- Jenab, Mazda
- ORCID
- Kong, So Yeon
- Tran, Hao Quang
- Gewirtz, Andrew T.
- Fedirko, Veronika
- Tjønneland, Anne
- Olsen, Anja
- Overvad, Kim
- Affret, Aurélie
- Kaaks, Rudolf
- Boeing, Heiner
- Aleksandrova, Krasimira
- Trichopoulou, Antonia
- Kritikou, Maria
- Palli, Domenico
- Krogh, Vittorio
- Mattiello, Amalia
- Tumino, Rosario
- Naccarati, Alessio
- Peeters, Petra H.
- Weiderpass, Elisabete
- Sala, Núria
- Sánchez, María-José
- Barricarte, Aurelio
- Wareham, Nicholas J.
- Khaw, Kay-Tee
- Bradbury, Kathryn E.
- Freisling, Heinz
- Ferrari, Pietro
- Gunter, Marc J.
- Cross, Amanda J.
- Jenab, Mazda
- Venue
- Cancer Epidemiology, Biomarkers & Prevention
- Published
- 2016-02-01
- Volume
- 25
- Issue
- 2
- Pages
- 291-301
- ISSN
- 1055-9965 (ISSN-L)
- 1538-7755
- PMC
- PMC5576525
- OpenAlex
- W2236938929
- Cited by
- 34
- References
- 54
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 2
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Epidemiology Biomarkers & Prevention (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Rivm Repository (Netherlands National Institute for Public Health and the Environment) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Apollo
- Funders
- Wereld Kanker Onderzoek Fonds as part of the World Cancer Research Fund (WCRF) International Regular Grant Programme (2010–251)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- colorectal cancer, lipopolysaccharide, flagellin, serum antibodies, intestinal permeability, bacterial endotoxin, sex differences, chronic inflammation, oxidative stress, colorectal cancer risk
- MeSH terms
- Endotoxins, Europe, Female, Flagellin, Humans, Male, Prospective Studies, Risk Factors, Colorectal Neoplasms, Cohort Studies, Biomarkers, Nutrition Assessment
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