The online version of this article (doi:10.1186/s12916-017-0830-8) contains supplementary material, which is available to authorized users.
Veronika Fedirko and Mazda Jenab are joint corresponding authors.
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.
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.
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.
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.
Additional file 1: Table S1. Baseline dietary intakes and blood biomarkers of incident HCC cases and matched control subjects within the European Prospective Investigation into Cancer and Nutrition (EPIC) study from 1992 to 2010. Table S2 Mean (95% CI) anti-LPS and anti-flagellin immunoglobulin levels in controls by sex, age at blood collection, and other baseline characteristics. Table S3 Incidence rate ratios and 95% confidence intervals of hepatocellular carcinoma according to categories of individual serum anti-LPS and anti-flagellin immunoglobulin levels, EPIC study, 1992–2010. (DOCX 35 kb)12916_2017_830_MOESM1_ESM.docx
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- Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
Hao Quang Tran
Andrew T. Gewirtz
Petra H. Peeters
H. B. Bueno-de-Mesquita
José María Huerta Castaño
J. Ramón Quirós
Kathryn E. Bradbury
Konstantinos K. Tsilidis
- BioMed Central
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