Single nucleotide polymorphisms of Toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma.
Shi Minmin,Xu Xiaoqian,Chen Hao,Chen Hao,Shen Baiyong,Shen Baiyong,Deng Xiaxing,Deng Xiaxing,Xie Junjie,Zhan Xi,Zhao Jianquan,Jiang Songyao +11 more
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TLDR
It is suggested that the risk of hepatocellular carcinoma was associated with TLR4 sequence variation, and single nucleotide polymorphisms ofTLR4 may play an important protective role in the development of liver cancer.Abstract:
Background
Toll-like receptor 4 (TLR4) is a key innate immunity receptor that initiates an inflammatory response. Growing evidence suggests that mutation of TLR4 gene may play a role in the development of cancers. This study aimed to investigate the temporal relationship of single nucleotide polymorphisms of TLR4 and the risk of hepatocellular carcinoma, a single center-based case-control study was conducted.
Methods
A systematic genetic analysis of sequence variants of TLR4 by evaluating ten single-nucleotide polymorphisms was performed from 216 hepatocellular carcinoma cases and 228 controls.
Results
Six single nucleotide polymorphisms of the TLR4 in the 5′-untranslated region and intron were associated with risk of hepatocellular carcinoma. Individuals carrying the heterozygous genotypes for the rs10759930, rs2737190, rs10116253, rs1927914, rs12377632 and rs1927911 had significantly decreased risk of hepatocellular carcinoma (adjusted odds ratio [OR], from 0.527 to 0.578, P<0.01) comparing with those carrying wild-type homozygous genotypes. In haplotype analysis, one haplotype (GCCCTTAG) of TLR4 was associated significantly with decrease of the occurrence of hepatocellular carcinoma (OR, 0.556, 95% confidence interval [CI], 0.407–0.758, P = 0.000).
Conclusions
Collectively, these results suggested that the risk of hepatocellular carcinoma was associated with TLR4 sequence variation. TLR4 single nucleotide polymorphisms may play an important protective role in the development of hepatocellular carcinoma.read more
Citations
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The Yin and Yang of Toll-like receptors in cancer
TL;DR: The dichotomous role of TLRs in tumor biology is reviewed in detail, focusing on relevant TLR-dependent pro- and antitumor pathways, and clinical applications ofTLR-targeted therapies for tumor prevention and treatment are discussed.
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TL;DR: Current knowledge about the TLR polymorphisms, their impact on TLR signaling, and associations with various inflammatory, infectious, allergic diseases and cancers are summarized, and the directions of future scientific research are discussed.
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TL;DR: Significant elevated risk was observed to be associated with G allele in gastric cancer and 'other cancers' in stratified analyses by cancer type for SNP rs4986790, indicating that polymorphisms in TLR4 may play a role, although modest, in cancer development.
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Heterogeneity of hepatocellular carcinoma contributes to cancer progression.
TL;DR: The heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.
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The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility
Xie Junjie,Jiang Songyao,Shi Minmin,Song Yanyan,Shen Baiyong,Deng Xiaxing,Jin Jiabin,Zhan Xi,Chen Hao +8 more
TL;DR: These results suggested that TLR2 rs3804099 C/T and rs3804100 C/C/T polymorphisms were closely associated with HCC and the haplotypes composed of these twoTLR2 synonymous SNPs have stronger effects on the susceptibility of HCC.
References
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