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Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, Shui IM, Chen YC - PLoS ONE (2014)

Bottom Line: Using 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Background: Toll-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.

Methods: We 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.

Results: Using 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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Related in: MedlinePlus

The role of TLR4 in innate immunity.TLR4 receptors are responsible for the recognition of bacterial lipopolysaccharide (LPS) monomers and partially oxidized LDL (oLDL) on innate immune cells. LPS monomers and oLDL bind to sites on the protein, CD14. CD14 promotes the binding of these ligands to the TLR4-MD-2 complex, which signals the activation of the nuclear factor kappa B (NF-κB) pathway. NF-κB products enter the nucleus and result in transcription followed by the production of cytokines and the activation of multiple inflammatory pathways. This figure was adapted from DeFranco et al. [48].
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pone-0110569-g004: The role of TLR4 in innate immunity.TLR4 receptors are responsible for the recognition of bacterial lipopolysaccharide (LPS) monomers and partially oxidized LDL (oLDL) on innate immune cells. LPS monomers and oLDL bind to sites on the protein, CD14. CD14 promotes the binding of these ligands to the TLR4-MD-2 complex, which signals the activation of the nuclear factor kappa B (NF-κB) pathway. NF-κB products enter the nucleus and result in transcription followed by the production of cytokines and the activation of multiple inflammatory pathways. This figure was adapted from DeFranco et al. [48].

Mentions: TLR4 recognizes pathogen-associated molecular patterns, i.e. LPS [46]. Damage-associated molecular pattern molecules may also interact with TLR4, i.e. oxidized low-density lipoprotein (LDL) [49], one of the atherogenic lipoproteins associated with atherosclerosis [50] and insulin resistance [51], [52]. Their interaction leads to the initiation of inflammatory response via NF-κB (Figure 4) [53]. TLR4 can also promote PCa development through releasing inflammatory mediators. Associations between TLR4 SNPs and PCa have been examined in several studies, though discordant data have been reported. However, the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. Thus, we performed a systematic review and meta-analysis of candidate-gene studies and GWASs analyzing this relationship and restricted to samples taken from European ancestry.


Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

Weng PH, Huang YL, Page JH, Chen JH, Xu J, Koutros S, Berndt S, Chanock S, Yeager M, Witte JS, Eeles RA, Easton DF, Neal DE, Donovan J, Hamdy FC, Muir KR, Giles G, Severi G, Smith JR, Balistreri CR, Shui IM, Chen YC - PLoS ONE (2014)

The role of TLR4 in innate immunity.TLR4 receptors are responsible for the recognition of bacterial lipopolysaccharide (LPS) monomers and partially oxidized LDL (oLDL) on innate immune cells. LPS monomers and oLDL bind to sites on the protein, CD14. CD14 promotes the binding of these ligands to the TLR4-MD-2 complex, which signals the activation of the nuclear factor kappa B (NF-κB) pathway. NF-κB products enter the nucleus and result in transcription followed by the production of cytokines and the activation of multiple inflammatory pathways. This figure was adapted from DeFranco et al. [48].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215920&req=5

pone-0110569-g004: The role of TLR4 in innate immunity.TLR4 receptors are responsible for the recognition of bacterial lipopolysaccharide (LPS) monomers and partially oxidized LDL (oLDL) on innate immune cells. LPS monomers and oLDL bind to sites on the protein, CD14. CD14 promotes the binding of these ligands to the TLR4-MD-2 complex, which signals the activation of the nuclear factor kappa B (NF-κB) pathway. NF-κB products enter the nucleus and result in transcription followed by the production of cytokines and the activation of multiple inflammatory pathways. This figure was adapted from DeFranco et al. [48].
Mentions: TLR4 recognizes pathogen-associated molecular patterns, i.e. LPS [46]. Damage-associated molecular pattern molecules may also interact with TLR4, i.e. oxidized low-density lipoprotein (LDL) [49], one of the atherogenic lipoproteins associated with atherosclerosis [50] and insulin resistance [51], [52]. Their interaction leads to the initiation of inflammatory response via NF-κB (Figure 4) [53]. TLR4 can also promote PCa development through releasing inflammatory mediators. Associations between TLR4 SNPs and PCa have been examined in several studies, though discordant data have been reported. However, the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. Thus, we performed a systematic review and meta-analysis of candidate-gene studies and GWASs analyzing this relationship and restricted to samples taken from European ancestry.

Bottom Line: Using 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

ABSTRACT

Background: Toll-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.

Methods: We 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.

Results: Using 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.

Show MeSH
Related in: MedlinePlus