Literature DB >> 26823475

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

So Yeon Kong1, Hao Quang Tran2, Andrew T Gewirtz2, Gail McKeown-Eyssen3, Veronika Fedirko4, Isabelle Romieu1, Anne Tjønneland5, Anja Olsen5, Kim Overvad6, Marie-Christine Boutron-Ruault7, Nadia Bastide7, Aurélie Affret7, Tilman Kühn8, Rudolf Kaaks8, Heiner Boeing9, Krasimira Aleksandrova9, Antonia Trichopoulou10, Maria Kritikou11, Effie Vasilopoulou12, Domenico Palli13, Vittorio Krogh14, Amalia Mattiello15, Rosario Tumino16, Alessio Naccarati17, H B Bueno-de-Mesquita18, Petra H Peeters19, Elisabete Weiderpass20, J Ramón Quirós21, Núria Sala22, María-José Sánchez23, José María Huerta Castaño24, Aurelio Barricarte25, Miren Dorronsoro26, Mårten Werner27, Nicholas J Wareham28, Kay-Tee Khaw29, Kathryn E Bradbury30, Heinz Freisling1, Faidra Stavropoulou1, Pietro Ferrari1, Marc J Gunter31, Amanda J Cross31, Elio Riboli31, W Robert Bruce32, Mazda Jenab33.   

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. ©2016 American Association for Cancer Research.

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Year:  2016        PMID: 26823475      PMCID: PMC5576525          DOI: 10.1158/1055-9965.EPI-15-0798

Source DB:  PubMed          Journal:  Cancer Epidemiol Biomarkers Prev        ISSN: 1055-9965            Impact factor:   4.254


  53 in total

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