Association between C13ORF31, NOD2, RIPK2 and TLR10 polymorphisms and urothelial bladder cancer

Hum Immunol. 2012 Jun;73(6):668-72. doi: 10.1016/j.humimm.2012.03.006. Epub 2012 Apr 12.

Abstract

Several evidences have been published linking polymorphism in genes involved in chronic or recurrent inflammation with increased tumor risk and progression. Nevertheless the influence of innate immune receptors in urothelial cancer risk and characteristics has not been sufficient explored. We studied the possible association of polymorphisms in genes encoding NOD2, RIPK2, TLR10 and C13ORF31 with the risk, clinical/pathological characteristics and outcomes of urothelial cancer. We have found association between RIPK2 (rs42490) and cancer risk (AA vs AT&TT, p=0042). In addition, we found statistical differences in TLR10 (rs4129009) gen between low and high tumor infiltration stage (p=0.033). NOD2 (rs9302752) and RIPK2 (rs42490) were found to be associated with development of lymph node metastasis (p=0.011 and p=0.015). Importantly we detect association of TLR10 (Log Rank=0.035) and RIPK2 (Log Rank=0040) with overall survival. Multivariate Cox analysis revealed that both SNPs were survival prognosis factor independent of tumor stage and grade. Our results indicate that innate immunity receptors play a role in modulating urothelial cancer risk and progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Immunity, Innate / genetics
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / immunology
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics*
  • Nod2 Signaling Adaptor Protein / immunology
  • Polymorphism, Genetic
  • Prognosis
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / immunology
  • Risk
  • Survival Analysis
  • Toll-Like Receptor 10 / genetics*
  • Toll-Like Receptor 10 / immunology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / immunology
  • Urothelium / metabolism
  • Urothelium / pathology*

Substances

  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • TLR10 protein, human
  • Toll-Like Receptor 10
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2