title: Single nucleotide polymorphisms of Toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma.
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.
authors.affiliation: Research Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shi
authors.initials: S
authors.lastname: Minmin
authors.forename: Xu
authors.initials: X
authors.lastname: Xiaoqian
authors.forename: Chen
authors.initials: C
authors.lastname: Hao
authors.forename: Shen
authors.initials: S
authors.lastname: Baiyong
authors.forename: Deng
authors.initials: D
authors.lastname: Xiaxing
authors.forename: Xie
authors.initials: X
authors.lastname: Junjie
authors.forename: Zhan
authors.initials: Z
authors.lastname: Xi
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jianquan
authors.forename: Jiang
authors.initials: J
authors.lastname: Songyao
mesh_terms: D020121:5' Untranslated Regions; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4