Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

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Title: Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
Authors: Fedirko, V
Hao, QT
Gewirtz, AT
Stepien, M
Trichopoulou, A
Aleksandrova, K
Olsen, A
Tjonneland, A
Overvad, K
Carbonnel, F
Boutron-Ruault, M-C
Severi, G
Kuhn, T
Kaaks, R
Boeing, H
Bamia, C
Lagiou, P
Grioni, S
Panico, S
Palli, D
Tumino, R
Naccarati, A
Peeters, PH
Bueno-de-Mesquita, HB
Weiderpass, E
Castano, JMH
Barricarte, A
Sanchez, M-J
Dorronsoro, M
Quiros, JR
Agudo, A
Sjoberg, K
Ohlsson, B
Hemmingsson, O
Werner, M
Bradbury, KE
Khaw, K-T
Wareham, N
Tsilidis, KK
Aune, D
Scalbert, A
Romieu, I
Riboli, E
Jenab, M
Item Type: Journal Article
Abstract: Background: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. Methods: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Results: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70–81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. Conclusions: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
Issue Date: 4-Apr-2017
Date of Acceptance: 3-Mar-2017
URI: http://hdl.handle.net/10044/1/48095
DOI: https://dx.doi.org/10.1186/s12916-017-0830-8
ISSN: 1741-7015
Journal / Book Title: BMC MEDICINE
Volume: 15
Issue: 1
Copyright Statement: © 2017 The Author(s). Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Hepatocellular carcinoma
Prospective studies
Hepatocellular carcinoma
Prospective studies
General & Internal Medicine
11 Medical And Health Sciences
Publication Status: Published
Article Number: ARTN 72
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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