Bacterial Translocation and Risk of Liver Cancer in a Finnish Cohort

Abstract

Background: Elevated systemic exposure to gut-derived bacterial products has been associated with hepatic inflammation and chronic liver diseases, potentially increasing the risk of liver cancer. However, only one prior study prospectively examined exposure to bacterial products in the circulation and risk of liver cancer, with a relatively limited coverage of biomarkers. Methods: We conducted a nested case-control study (224 liver cancer cases and 224 matched controls) in a large cohort of Finnish male smokers followed from baseline (1985-1988) to 2014. The associations between a panel of biomarkers for bacterial translocation and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression. The biomarkers included immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and the LPS-binding protein. Results: Anti-flagellin IgA [odds ratios (OR), 2.79; 95% confidence intervals (CI), 1.34-5.78; P trend ¼ 0.01] and anti-LPS IgA (2.44; 95% CI, 1.33-4.48; P trend < 0.01) were significantly associated with risk of liver cancer. When restricting the analysis to histologically classified hepatocellular carcinoma, the ORs were 4.18 (95% CI, 1.60-10.92; P trend < 0.01) and 2.48 (95% CI, 1.16-5.29; P trend < 0.01), respectively. The results were not substantially changed after excluding cases diagnosed within the first 5 years of follow-up and those with hepatitis C virus infection. Conclusions: Antibodies to flagellin and LPS were associated with increased risk of liver cancer. Impact: Gut-derived bacterial translocation into the circulation may play a role in the development of primary liver cancer. Our findings could contribute to the understanding of primary liver cancer etiology and further prevention efforts.

Identification of Aberrantly Methylated Differentially CpG Sites in Hepatocellular Carcinoma and Their Association With Patient Survival

“…We further divided the LIHC cohort into high expression and low expression groups according to the median value of the LBP gene expression level and analyzed the differentially expressed genes between these two groups. Gene Ontology and KEGG analysis suggested that these genes clustered in acute-phase response and inflammatory response ( P < 0.01), which implied that LBP in live cancer cells may engage in the local immune response to gut-derived bacterial translocation, which was an etiological factor of HCC according to current reports ( 29 , 30 ). The association of LBP and clinicopathological parameters was further investigated by analyzing the LIHC cohort from TCGA.…”

“…that LBP in live cancer cells may engage in the local immune response to gut-derived bacterial translocation, which was an etiological factor of HCC according to current reports (29,30). The association of LBP and clinicopathological parameters was further investigated by analyzing the LIHC cohort from TCGA.…”

Epigenetic reprogramming in periodontal disease: Dynamic crosstalk with potential impact in oncogenesis

“…This acute inflammatory response turns to a chronic stage when the antigen-presenting cells become involved and present the antigens/microorganisms to immunocompetent cells expanding the antibody-secreting plasma cell population viral infection. [47][48][49][50] In 2007, our investigations in a murine model showed the promotion of DNA hypermethylation patterns in response to periodontal pathogen infection, where we found that The positive correlation between several inflammatory markers, epigenome, and gene expression, has been reported not only for US but also for other populations. 15,32,34,35 In a study evaluating methylation patterns in aggressive periodontitis cases, the DNA CpG methylation patterns of 22 inflammatory genes, collected from gingival biopsies taken from healthy patients and patients with aggressive periodontitis, showed higher methylation levels of CCL25 and interleukin-17C genes in healthy gingival tissue compared with periodontitis-affected tissue.…”

“…Recent progress in inflammation‐associated cancer research has unveiled the associations between chronic inflammatory conditions and carcinogenesis, through epidemiological data pointing to a correlation between the chronic inflammatory/infectious condition and a higher incidence of several types of cancer . There is also clear evidence showing specific microbial infection as a key contributing factor to the progress of various cancer types such as Helicobacter pylori ‐associated gastric cancer and hepatitis C virus‐positive liver carcinoma …”

“…[58][59][60][61][62] There is also clear evidence showing specific microbial infection as a key contributing factor to the progress of various cancer types such as Helicobacter pylori-associated gastric cancer and hepatitis C virus-positive liver carcinoma. [47][48][49][50]63 The inflammation-associated cancers have been linked to the interaction between microbial infection, either bacterial or viral, and inflammatory response mediators such as cytokines, reactive oxygen species, reactive nitrogen species, and growth factors, including vascular endothelial growth factor and epidermal growth factor. [64][65][66][67] As a consequence, genetic and epigenetic changes in various protooncogenes and tumor-suppressor genes have been detected.…”