Toll-like receptor 3 genetic variants and susceptibility to hepatocellular carcinoma and HBV-related hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate whether TLR3 polymorphisms were associated with susceptibility to HCC. Two polymorphisms in the TLR3 gene, -976T/A and +1234C/T, were tested by polymerase chain reaction-restriction fragment length polymorphism in 466 HCC patients and 482 healthy controls. Results showed that the prevalence of +1234CT genotype and +1234TT genotype were significantly increased in the HCC cases than in controls (odds ratio [OR] =1.51; 95 % confidence interval [CI]; 1.22-1.93; p=0.004 and OR=3.19; 95 % CI, 1.82-5.39; p=1.99 × 10(-5), respectively). The -976T/A polymorphism did not reveal any differences between cases and controls. When analyzing the TLR3 +1234C/T polymorphism with different clinical parameters in HCC patients, the cases who were hepatitis B virus (HBV) carriers had higher number of +1234CT genotype and +1234T allele than those without HBV infection (p=0.032 and p=0.043). These data indicate that TLR3 +1234C/T polymorphism could be a novel risk factor for HCC, especially the HBV-related HCC.

Genetic polymorphisms in Toll-like receptor 3 gene are associated with the risk of hepatitis B virus-related liver diseases in a Chinese population

“…Genetic variations in TLR3 have been correlated with susceptibility to various diseases, including CHB and HCC. Previous studies reported that the TLR3 C1234T polymorphism was associated with increased susceptibility to CHB (Rong et al, 2013), as well as HCC (Li and Zheng, 2013). The present study demonstrated that the TLR3 rs3775290 polymorphism was associated with a decreased risk for CHB, HBV-related LC, and HCC.…”

“…Genetic variations in TLR3 have been correlated with susceptibility to various diseases, including viral hepatitis and HCC (He et al, 2007;Ishizaki et al, 2008;Etem et al, 2011;Al-Qahtani et al, 2012;Sironi et al, 2012;Lee et al, 2013;Li and Zheng, 2013;Rong et al, 2013). However, little is known concerning TLR3 gene polymorphisms and HBVrelated CHB, LC, and HCC.…”

The toll-like receptor 3 pathway in homeostasis, responses to injury and wound repair

“…HSC also undergo transformation into myofibroblasts, leading to increased production of extracellular matrix proteins; this process is a host-protective response, but causes scarring and liver fibrosis when dysregulated [79]. As noted above, TLR3 signalling has been implicated in host responses during HBV infection [40][41][42]. However, growing evidence suggests that TLR3 also contributes to the inactivation or death of activated HSC and Kupffer cells during liver injury, contributing to protective responses against liver damage [80] and fibrosis [81,82].…”

“…Tlr3 -/-mice displayed enhanced replication of HSV-1 in the CNS [38], and an increased susceptibility to HSV-2 infection in the CNS after vaginal inoculation [39]. In humans, TLR3 polymorphisms (C1234T, rs1879026 G/T) have also been linked to increased risk to chronic hepatitis B virus (HBV) infection and HBV-induced hepatocellular carcinoma [40,41], while the C13766T TLR3 polymorphism was suggested to be protective against HBV infection and HBV-related liver disease [42]. A study analysing Saudi Arabian patients with HBV infections reported a TLR3 single nucleotide polymorphism (rs1879026 G/T) that was found more frequently in HBV-infected patients [40].…”

Prognostic Value of Genetic Markers for Efficacy Estimation of Induction Treatment Including Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients

“…Рецептор, кодируемый этим геном, способен связывать двухцепочечную РНК [127]. При поиске взаимосвязи полиморфизма гена TLR3 с разви-тием злокачественных новообразований корреляции не обнаружено [119,[128][129][130][131][132][133][134][135][136].…”