Toll-like receptor-associated sequence variants and prostate cancer risk among men of African descent

Genes Immun. 2013 Sep;14(6):347-55. doi: 10.1038/gene.2013.22. Epub 2013 May 9.

Abstract

Recent advances demonstrate a relationship between chronic/recurrent inflammation and prostate cancer (PCA). Among inflammatory regulators, toll-like receptors (TLRs) have a critical role in innate immune responses. However, it remains unclear whether variant TLR genes influence PCA risk among men of African descent. Therefore, we evaluated the impact of 32 TLR-associated single-nucleotide polymorphisms (SNPs) on PCA risk among African Americans and Jamaicans. SNP profiles of 814 subjects were evaluated using Illumina's Veracode genotyping platform. Single and combined effects of SNPs in relation to PCA risk were assessed using age-adjusted logistic regression and entropy-based multifactor dimensionality reduction (MDR) models. Seven sequence variants detected in TLR6, TOLLIP (Toll-interacting protein), IRAK4 (interleukin-1 receptor-associated kinase 4) and IRF3 (interferon regulatory factor 3) were marginally related to PCA. However, none of these effects remained significant after adjusting for multiple hypothesis testing. Nevertheless, MDR modeling revealed a complex interaction between IRAK4 rs4251545 and TLR2 rs1898830 as a significant predictor of PCA risk among US men (permutation testing P-value=0.001). However, these findings require further assessment and validation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics*
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Interferon Regulatory Factor-3 / genetics
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / genetics*
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 6 / genetics*

Substances

  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Intracellular Signaling Peptides and Proteins
  • TLR2 protein, human
  • TLR6 protein, human
  • TOLLIP protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases