Opisthorchiasis with proinflammatory cytokines (IL-1β and TNF-α) polymorphisms influence risk of intrahepatic cholangiocarcinoma in Thailand: a nested case-control study

Abstract

BackgroundChronic inflammation and repeated infection with Opisthorchis viverrini (O. viverrini) induces intrahepatic cholangiocarcinoma (ICC). Inflammatory cytokines such as interleukin (IL) and tumor necrosis factor (TNF) are substances in the immune system that promote inflammation and causes disease to progress. Genes that help express proinflammatory cytokines can affect an individual’s susceptibility to disease, especially in cancer-related chronic inflammation. This study aimed to investigate risk factors for ICC with a focus on opisthorchiasis and polymorphisms of proinflammatory cytokines (IL-1β and TNF-α).MethodsThis study was a nested case-control study within a cohort study. 219 subjects who developed a primary ICC were identified and matched with two non-cancer controls from the same cohort based on sex and age at recruitment (±3 years). An O. viverrini-IgG antibody was assessed using enzyme linked immunosorbent assay. IL-1β and TNF-α polymorphisms were analyzed using a polymerase chain reaction with high resolution melting analysis. Associations between variables and ICC were assessed using conditional logistic regression.ResultsSubjects with a high infection intensity had higher risk of ICC than those who had a low level (OR = 2.1; 95% CI: 1.2–3.9). Subjects with all genotypes of TNF-α (GG, GA, AA) and high infection intensity were significantly related to an increased risk of ICC (p < 0.05).ConclusionsPolymorphisms of IL-1β and TNF-α are not a risk of ICC, but an individual with O. viverrini infection has an effect on all genotypes of the TNF-α gene that might promote ICC. Primary prevention of ICC in high-risk areas is based on efforts to reduce O. viverrini infection.

The Functional Roles of Immune Cells in Primary Liver Cancer

“…42 TNF-a elevates the expression of activation-induced cytidine deaminase, a mutation-generating enzyme, leading to higher mutation numbers in tumor suppressor genes, such as p16 and p53, leading to CCA development. 43 Previous studies suggest that specific polymorphisms in the TNF-a gene contribute to the development of CCA, 44 indicating the association of TNF-a with liver cancer. CCL2 binds to CCR2 and functions as a proinflammatory cytokine as well as a chemokine promoting macrophage infiltration.…”

Clonorchis sinensis aggravates biliary fibrosis through promoting IL-6 production via toll-like receptor 2-mediated AKT and p38 signal pathways

“…sinensis infection. In addition, other liver flukes infection, such as Opisthorchis viverrini , also result in high expression of IL-6 and TNF-α, and is closely associated with the development of liver fibrosis [ 32 , 33 ]. Whether the synergistic regulation of TLR2 and TLR4 is also applicable to the pathogenic process of O .…”

“…It was suggested that both TLR2 and TLR4 could regulate the cytokine release in mice induced by C. sinensis infection. In addition, other liver flukes infection, such as Opisthorchis viverrini, also result in high expression of IL-6 and TNF-α, and is closely associated with the development of liver fibrosis [32,33]. Whether the synergistic regulation of TLR2 and TLR4 is also applicable to the pathogenic process of O. viverrini deserves further investigation in future studies, which may provide more possibilities to unravel liver fibrosis in liver flukes.…”

Association between <b><i>Opisthorchis viverrini</i></b> Infection and Glomerular Disease in Thailand

“…There is evidence that parasitic infection, particularly schistosomiasis, malaria, filariasis, and leishmaniasis, are associated with the development of glomerulonephritis (GN) [8, 9], but the need to clarify the role of Opisthorchiasis remains. In addition to hepatobiliary inflammation and cholangiocarcinoma, chronic OV infection results in the dysregulation of systemic immune response and cytokine production [10, 11], both of which are crucial mechanisms in the pathogenesis of immune-mediated GN. Kalyuzhina and Kalyuzhin [12] demonstrated that chronic GN patients with concomitant chronic OV infection had a significantly higher levels of immunoglobulin G (IgG), IgE, and circulating immune complex as compared to chronic GN patients without OV infection.…”