Serum endotoxins and flagellin and risk of colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC) cohort

So Yeon Kong, Hao Quang Tran, Andrew T. Gewirtz, Gail McKeown-Eyssen, Veronika Fedirko, Isabelle Romieu, Anne Tjønneland, Anja Olsen, Kim Overvad, Marie Christine Boutron-Ruault, Nadia Bastide, Aurélie Affret, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Maria Kritikou, Effie Vasilopoulou, Domenico PalliVittorio Krogh, Amalia Mattiello, Rosario Tumino, Alessio Naccarati, H. B. Bueno-De-mesquita, Petra H. Peeters, Elisabete Weiderpass, J. Ramón Quirós, Núria Sala, María José Sánchez, José María Huerta Castanõ, Aurelio Barricarte, Miren Dorronsoro, Marten Werner, Nicholas J. Wareham, Kay Tee Khaw, Kathryn E. Bradbury, Heinz Freisling, Faidra Stavropoulou, Pietro Ferrari, Marc J. Gunter, Amanda J. Cross, Elio Riboli, W. Robert Bruce, Mazda Jenab

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)291-301
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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., ... Jenab, M. (2016). Serum endotoxins and flagellin and risk of colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC) cohort. Cancer Epidemiology Biomarkers and Prevention, 25(2), 291-301. https://doi.org/10.1158/1055-9965.EPI-15-0798