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

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

Author information

1
Department of Pharmacology and Toxicology, University of Louisville, Clinical and Translational Research Building, 505 South Hancock Street, Room 306, Louisville, KY 40202, USA.

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.

PMID:
23657238
PMCID:
PMC3743959
DOI:
10.1038/gene.2013.22
[Indexed for MEDLINE]
Free PMC Article

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