Sequence Variants of Toll-Like Receptor 4 and Susceptibility to Prostate Cancer

Chen, Yen‐Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J.

doi:10.1158/0008-5472.can-05-2078

Cited by 161 publications

(156 citation statements)

References 38 publications

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“…17 Furthermore, a singlenucleotide polymorphism in TLR4 gene is associated with an elevated risk of prostate cancer. 26 By inference, TLR4 may play a role in tumorigenesis. Mice with functional Tlr4 have reduced tumor formation, 27 but conversely TLR4 was found to facilitate tumor cells to escape from immune surveillance.…”

Section: Discussionmentioning

confidence: 99%

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Tichomirowa

Theodoropoulou

Daly

et al. 2008

Intl Journal of Cancer

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Meningiomas are the second most common type of brain and CNS tumors by histology. Surgery and radiotherapy are main treatment options, but meningiomas may be impossible to adequately resect or may regrow after surgery. In spite of many experimental attempts, there is no generally accepted chemotherapeutic approach. We have studied in a series of meningiomas the expression of the Toll-like receptor 4 (TLR4), which apart from its major role as a key factor of the innate immune system, is believed to play a role in tumorigenesis. All meningiomas studied expressed TLR4 mRNA and protein at variable degree. Paclitaxel, a ligand of TLR4, exhibited a dose-and time-dependent growth suppression in both monolayer and spheroid meningioma cell cultures. The knockdown of TLR4 with siRNA in meningioma cell cultures abrogated the inhibitory effect of paclitaxel. The suppressive action of paclitaxel on meningioma cell growth was enhanced in the presence of fluvastatin or the mitogen-actvated protein kinase (ERK1/2) inhibitor PD98059. At least part of the growth suppressive effect was mediated by the induction of apoptosis in meningioma cells by paclitaxel alone or in combination with fluvastatin. In conclusion, our in vitro results suggest that paclitaxel alone or in combination with other inhibitors of cell growth (statins, MAPK inhibitors) could provide a potential tool for the treatment of TLR4 expressing meningiomas.

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Section: Discussionmentioning

confidence: 99%

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Tichomirowa

Theodoropoulou

Daly

et al. 2008

Intl Journal of Cancer

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“…After reviewing all possibly eligible papers, we finally included 12 eligible studies from 13 papers (Zheng et al, 2004;Chen et al, 2005;Cheng et al, 2007a;Wang et al, 2009;Hishida et al, 2009Hishida et al, , 2011Kupcinskas et al, 2011;Shi et al, 2011;Kim et al, 2012;Shui et al, 2012;He et al, 2013;Companioni et al, 2014;Li et al, 2014) in the present meta-analysis. A flow chart of the literature search is presented in Figure 1.…”

Section: Study Searchmentioning

confidence: 99%

“…Among the six studies of prostate cancer (Zheng et al, 2004;Chen et al, 2005;Cheng et al, 2007a;Wang et al, 2009;Kim et al, 2012;Shui et al, 2012), two showed a statistically significant association between rs11536889 and prostate cancer risk, with ORs of 1.26 and 1.99, respectively. Only one study was on hepatocellular cancer, and it failed to show a positive outcome (Shi et al, 2011).…”

Section: Systematic Review Of Studiesmentioning

confidence: 99%

Pooled analysis of association between a genetic variant in the 3'-untranslated region of Toll-like receptor 4 and cancer risk

Wang

Miao

2015

Genet. Mol. Res.

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ABSTRACT. Many epidemiological studies have shown the association between certain genetic variations in the Toll-like receptor 4 (TLR4) gene (for example, rs4986790 and rs4986791) and cancer risk. However, the results from investigations into the association between rs11536889, a genetic variant in the 3'-untranslated region of TLR4, and cancer risk lack consensus. We performed a meta-analysis to investigate the effect of rs11536889 on cancer risk. A total of 12 relevant case-control studies were included in this analysis (6222 cases and 7948 controls). The pooled ORs with their corresponding 95%CIs were estimated. We did not detect any association between rs11536889 and overall cancer risk (P = 0.13). However, stratification analysis by cancer type revealed a borderline statistically significant increased risk in both genotype comparison (OR for the variant genotype in the dominant model = 1.17; 95%CI = 0.98-1.40; P = 0.08) and allele comparison (OR for variant allele = 1.14; 95%CI = 0.99-1.32; P = 0.07) for prostate cancer. In contrast, no statistically significant or borderline result was found for gastric cancer. These findings indicate that rs11536889 in TLR4 might be specifically associated with prostate 17848 X. Wang et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17847-17855 (2015) cancer. However, owing to the modest and underpowered results, and the limitations of the original studies included for analysis, further prospective studies with larger sample sizes are required to confirm our findings.

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“…Similarly, mutations in some TLRs appear to change the NF-kB response of individuals to certain pathogens (Orange et al, 2005) or be associated with an increased risk of certain cancers (Chen et al, 2005b). Much less studied are the roles of mutations either in NF-kB gene promoters (e.g., NFKB1) or in kB sites in NF-kB target gene promoters in human disease susceptibility, although such correlations have been noted (see Table 3).…”

Section: Other Human Disease Mutations Associated With Nf-jb Signalingmentioning

confidence: 99%

Mutations in the NF-κB signaling pathway: implications for human disease

2006

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Sequence Variants of Toll-Like Receptor 4 and Susceptibility to Prostate Cancer

Cited by 161 publications

References 38 publications

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Toll‐like receptor‐4 is expressed in meningiomas and mediates the antiproliferative action of paclitaxel

Pooled analysis of association between a genetic variant in the 3'-untranslated region of Toll-like receptor 4 and cancer risk

Mutations in the NF-κB signaling pathway: implications for human disease

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