Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

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Title: Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
Authors: Kong, SY
Hao, QT
Gewirtz, AT
McKeown-Eyssen, G
Fedirko, V
Romieu, I
Tjonneland, A
Olsen, A
Overvad, K
Boutron-Ruault, M-C
Bastide, N
Affret, A
Kuehn, 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, HB
Peeters, PH
Weiderpass, E
Ramon Quiros, J
Sala, N
Sanchez, M-J
Huerta Castano, JM
Barricarte, A
Dorronsoro, M
Werner, M
Wareham, NJ
Khaw, K-T
Bradbury, KE
Freisling, H
Stavropoulou, F
Ferrari, P
Gunter, MJ
Cross, AJ
Riboli, E
Bruce, WR
Jenab, M
Item Type: Journal Article
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.
Issue Date: 11-Jan-2016
Date of Acceptance: 11-Dec-2015
ISSN: 1538-7755
Publisher: American Association for Cancer Research
Start Page: 291
End Page: 301
Journal / Book Title: Cancer Epidemiology Biomarkers & Prevention
Volume: 25
Issue: 2
Copyright Statement: © 2016 American Association for Cancer Research.
Sponsor/Funder: Commission of the European Communities
University Medical Center Utrecht
Imperial College Trust
Funder's Grant Number: SP23-CT-2005-006438
Keywords: Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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