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

• 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)
• Journal Title: Cancer Epidemiology, Biomarkers and Prevention
• Volume: Volume 25, Number 2
• Publisher: American Association for Cancer Research | 2016-02, Pages 291-301
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1158/1055-9965.EPI-15-0798
• Subjects: Health Sciences, Oncology; Health Sciences, Nutrition; Health Sciences, Public Health
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Public, Environmental & Occupational Health; C-REACTIVE PROTEIN; IMMUNE-RESPONSE; BACTERIAL FLAGELLIN; BARRIER DEFECTS; TEXTILE WORKERS; CROHNS-DISEASE; GUT MICROBIOTA; RECTAL-CANCER; T-CELLS; COLON; Endotoxins; Flagellin; Colorectal cancer; European Prospective Investigation into Cancer and Nutrition (EPIC)

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.