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Toll-like receptor 4 gene polymorphism downregulates gene expression and involves in susceptibility to bladder cancer

Yizhen Shen1, Meimei Bu, Aimin Zhang

  • 1Department of Urology, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong, 250031, People's of Republic of China, yizhenshen@126.com.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|December 5, 2014
PubMed

Insights

Genetic variations in Toll-like receptor 4 (TLR4) are linked to bladder cancer risk. The TLR4 -729G/C polymorphism increases susceptibility by downregulating TLR4 gene expression in immune cells.

Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Bladder cancer is a significant health concern in China.
  • Toll-like receptor 4 (TLR4) plays a crucial role in immune responses.
  • Genetic polymorphisms can influence disease pathogenesis.

Purpose of the Study:

  • To investigate the association between TLR4 gene polymorphisms and bladder cancer risk in the Chinese population.
  • To examine the functional impact of these polymorphisms on TLR4 gene and protein expression in immune cells.

Main Methods:

  • Genotyping of TLR4 -729G/C and -260G/C polymorphisms in 282 bladder cancer patients and 298 healthy controls.
  • Quantification of TLR4 mRNA and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects with different genotypes.

Main Results:

  • The TLR4 -729G/C polymorphism was significantly associated with an increased risk of bladder cancer (OR=2.50, P=0.002).
  • Carriers of the -729GC genotype exhibited downregulated TLR4 mRNA and protein levels in CD4+ T cells, CD8+ T cells, and monocytes.
  • No significant correlation was found between the TLR4 -260G/C polymorphism and bladder cancer risk or gene expression.

Conclusions:

  • TLR4 genetic polymorphism, specifically the -729G/C variant, is associated with increased susceptibility to bladder cancer.
  • This increased risk may be mediated by the downregulation of TLR4 expression in key immune cells, potentially impairing immune surveillance.

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