Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Abstract

BackgroundToll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.MethodsWe performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.ResultsUsing random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.Conclusions TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.

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“…Despite certain claims that the association between the SNPs of TLR4 gene related sites (including rs11536896 and rs7873784) and cancer development demands in-depth research, no other loci have been found to have significant correlations with cancer (Kutikhin, 2011;Weng et al 2014). To the best our knowledge, it was the first study to investigate the association between two SNPs of TLR4 gene targeted by miR-140 and geneenvironment interaction with cervical precancerous lesions risk.…”

No increased risk of psoriasis in patients receiving androgen deprivation therapy for prostate cancer: a 17-year population-based study

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