Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

• Type of Material: Article
• Authors: So Yeon Kong, International Agency for Research on Cancer; Hao Quang Tran, Georgia State University; Andrew Gewirtz, Emory University; Gail McKeown-Eyssen, University of Toronto; Veronika Fedirko, Emory University; Isabelle Romieu, Emory University; Anne Tjonneland, Danish Cancer Society Research Center; Anja Olsen, Danish Cancer Society Research Center; Kim Overvad, Aarhus University; Marie-Christine Boutron-Ruault, INSERM; Nadia Bastide, INSERM; Aurelie Affret, INSERM; Tilman Kuhn, German Cancer Research Center (DKFZ); Rudolf Kaaks, German Cancer Research Center (DKFZ); Heiner Boeing, German Institute of Human Nutrition Potsdam-Rehbruecke; Krasimira Aleksandrova, German Institute of Human Nutrition Potsdam-Rehbruecke; Antonia Trichipoulou, Hellenic Health Foundation; Maria Kritikou, Hellenic Health Foundation; Effie Vasilopoulou, University of Athens Medical School; Domenico Palli, Cancer Research and Prevention Institute – ISPO; Vittorio Krogh, IRCCS Foundation; Amalia Mattiello, Federico II University; Rosario Tumino, “Civic – MP Arezzo” Hospital; Alessio Naccarati, Torino Molecular and Genetic Epidemiology Unit; H. Bas Bueno-de-Mesquita, National Institute for Public Health and Environment (RIVM), Bilthoven; Petra H. Peeters, University Medical Center Utrecht; Elisabete Weiderpass, University of Tromsø; J. Ramon Quiros, Public Health Directorate, Asturias; Nuria Sala, Catalan Institute of Oncology (IDIBELL); Maria-Jose Sanchez, Hospitales Universitarios de Granada/Universidad de Granada; Jose Maria Huerta Castano, CIBER de Epidemiología y Salud Pública (CIBERESP); Aurelio Barricarte, CIBER de Epidemiología y Salud Pública (CIBERESP); Miren Dorronsoro, Basque Regional Health Department; Marten Werner, Medicine Umeå University; Nicholas J. Wareham, Addenbrooke's Hospital; Kay-Tee Khaw, University of Cambridge; Kathryn E. Bradbury, University of Oxford; Heinz Freisling, International Agency for Research on Cancer (IARC-WHO); Faidra Stavropoulou, International Agency for Research on Cancer (IARC-WHO); Pietro Ferrari, International Agency for Research on Cancer (IARC-WHO); Marc J. Gunter, Imperil College London; Amanda J. Cross, Imperil College London; Elio Riboli, Imperil College London; W. Robert Bruce, University of Toronto; Mazda Jenab, International Agency for Research on Cancer (IARC-WHO)
• Language: English
• Date: 2016-02
• Publisher: American Association for Cancer Research
• Publication Version: Final Published Version
• Copyright Statement: © 2016 American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/1055-9965.EPI-15-0798
• Title of Journal or Parent Work: Cancer Epidemiology, Biomarkers and Prevention
• ISSN: 1055-9965
• Volume: 25
• Issue: 2
• Start Page: 291
• End Page: 301
• Grant/Funding Information: This work was funded by Wereld Kanker Onderzoek Fonds as part of the World Cancer Research Fund (WCRF) International Regular Grant Programme (grant number 2010-251; PI: M. Jenab).; The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); 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), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom).; The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer.
• Keywords: BACTERIAL FLAGELLIN; Public, Environmental & Occupational Health; TEXTILE WORKERS; C-REACTIVE PROTEIN; RECTAL-CANCER; Life Sciences & Biomedicine; GUT MICROBIOTA; Oncology; Flagellin; European Prospective Investigation into Cancer and Nutrition (EPIC); BARRIER DEFECTS; COLON; CROHNS-DISEASE; Endotoxins; Colorectal cancer; IMMUNE-RESPONSE; T-CELLS; Science & Technology
• Research Categories: Health Sciences, Nutrition; Health Sciences, Public Health; Health Sciences, Oncology

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.