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


ABSTRACT: 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.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.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).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.Further studies are warranted to better clarify these preliminary observations.

SUBMITTER: Kong SY 

PROVIDER: S-EPMC5576525 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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

Kong So Yeon SY   Tran Hao Quang HQ   Gewirtz Andrew T AT   McKeown-Eyssen Gail G   Fedirko Veronika V   Romieu Isabelle I   Tjønneland Anne A   Olsen Anja A   Overvad Kim K   Boutron-Ruault Marie-Christine MC   Bastide Nadia N   Affret Aurélie A   Kühn Tilman T   Kaaks Rudolf R   Boeing Heiner H   Aleksandrova Krasimira K   Trichopoulou Antonia A   Kritikou Maria M   Vasilopoulou Effie E   Palli Domenico D   Krogh Vittorio V   Mattiello Amalia A   Tumino Rosario R   Naccarati Alessio A   Bueno-de-Mesquita H B HB   Peeters Petra H PH   Weiderpass Elisabete E   Quirós J Ramón JR   Sala Núria N   Sánchez María-José MJ   Castaño José María Huerta JM   Barricarte Aurelio A   Dorronsoro Miren M   Werner Mårten M   Wareham Nicholas J NJ   Khaw Kay-Tee KT   Bradbury Kathryn E KE   Freisling Heinz H   Stavropoulou Faidra F   Ferrari Pietro P   Gunter Marc J MJ   Cross Amanda J AJ   Riboli Elio E   Bruce W Robert WR   Jenab Mazda M  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20160111 2


<h4>Background</h4>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.<h4>Methods</h4>A total of 1,065 incident colorectal cancer c  ...[more]

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