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Role of toll-like receptor 4 in colorectal carcinogenesis: a meta-analysis

Xiao-Xia Li1, Gong-Ping Sun1, Jin Meng1

  • 1Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.

Plos One
|April 8, 2014
PubMed
Abstract

Insights

Toll-like receptor 4 (TLR-4) gene polymorphisms, specifically the 399 C>T variant, are linked to increased colorectal cancer (CRC) risk, particularly in Asian populations. Elevated TLR-4 expression also correlates with CRC, suggesting its potential as an early diagnostic biomarker.

Area of Science:

  • Immunology
  • Oncology
  • Genetics

Background:

  • Colorectal cancer (CRC) is a significant global health concern.
  • Toll-like receptor 4 (TLR-4) is implicated in inflammatory and immune responses, potentially influencing carcinogenesis.
  • Understanding the genetic and expression-level roles of TLR-4 in CRC is crucial for developing diagnostic and therapeutic strategies.

Purpose of the Study:

  • To evaluate the association between toll-like receptor 4 (TLR-4) and colorectal carcinogenesis.
  • To investigate the role of specific TLR-4 gene polymorphisms (299 A>G and 399 C>T) in CRC risk.
  • To assess TLR-4 mRNA and protein expression levels in CRC patients compared to healthy controls.

Main Methods:

  • A comprehensive meta-analysis of fourteen case-control studies involving 1,209 CRC cases and 1,218 healthy controls.
  • Searched multiple databases (PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, CBM) from inception to November 2013.
  • Calculated odds ratios (ORs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) to assess associations.

Main Results:

  • The TLR-4 399 C>T polymorphism was significantly associated with an increased risk of CRC (allele model: OR=1.77, 95%CI=1.32–2.36; dominant model: OR=1.83, 95%CI=1.32–2.52).
  • No significant correlation was found between the TLR-4 299 A>G polymorphism and CRC risk.
  • Subgroup analysis revealed that TLR-4 polymorphisms increased CRC risk in Asians but not in Caucasians or Africans.
  • TLR-4 mRNA and protein levels were significantly higher in CRC patients than in healthy controls (SMD=2.51 for mRNA, OR=4.75 for protein).

Conclusions:

  • TLR-4 plays a significant role in colorectal carcinogenesis.
  • The TLR-4 399 C>T polymorphism is a potential genetic risk factor for CRC, particularly in Asian populations.
  • Elevated TLR-4 expression suggests it is a promising biomarker for the early diagnosis of CRC.

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