ArticleWorld journal of gastroenterology2015
TLR2 and TLR4 polymorphisms influence mRNA and protein expression in colorectal cancer.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Association between TLR2 polymorphisms (- 196-174 Ins/Del, R677W, R753Q, and P631H) and schizophrenia in a Tunisian population.Immunologic research · 2021Trial
- Gene Polymorphisms ofGenes · 2026Article
- Pathomorphological Manifestations and the Course of the Cervical Cancer Disease Determined by Variations in theDiagnostics (Basel, Switzerland) · 2023Article
- Identifying key genes of classic papillary thyroid cancer in women aged more than 55 years old using bioinformatics analysis.Frontiers in endocrinology · 2022Article
- Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility.BioMed research international · 2021Review
- Characterization and strong risk association ofWorld journal of gastrointestinal oncology · 2020Article
- Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.Frontiers in immunology · 2020Review
- Article
- Effect of TLR2 on the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer.Cancer cell international · 2020Article
- -196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects.Bioscience reports · 2019Article
- Relationship betweenWorld journal of gastroenterology · 2018Article
- TLR4 Polymorphisms and Expression in Solid Cancers.Molecular diagnosis & therapy · 2018Review
- Comprehensive assessment of association between TLR4 gene polymorphisms and cancer risk: a systematic meta-analysis.Oncotarget · 2017Article
- Customized laboratory TLR4 and TLR2 detection method from peripheral human blood for early detection of doxorubicin-induced cardiotoxicity.Cancer gene therapy · 2017Article
- Association of Polymorphisms inInternational journal of endocrinology · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo evaluate the effect of promoter region polymorphisms of toll-like receptor (TLR)2-196 to -174del and TLR4-1607T/C (rs10759932) on mRNA and protein expression in tumor tissue and of TLR4+896A/G (rs4986790) on colorectal cancer (CRC) risk.
methodsThe TLR2-196 to -174del polymorphism was investigated using allele-specific polymerase chain reaction (PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length polymorphism (RFLP). We genotyped 434 DNA samples from 194 CRC patients and 240 healthy individuals. The mRNA relative quantification (RQ) was performed in 40 tumor tissue samples by quantitative PCR TaqMan assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference genes were used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.
resultsNo association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models (log-additive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to -174del was associated with increased CRC risk [dominant: odds ratio (OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 mRNA expression was increased in tumor tissue (RQ = 2.36) when compared to adjacent normal tissue (RQ = 1; P < 0.0001), whereas the TLR4 mRNA showed a basal expression (RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of mRNA expression. In addition, the TLR2-196 to -174del variant carriers showed mRNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to -174del variant carriers [117 ± 10 arbitrary unit (a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4 -1607T/C polymorphism no significant difference was found for both mRNA (P = 0.56) and protein expression (P = 0.26).
conclusionOur findings suggest that TLR2-196 to -174del polymorphism increases TLR2 mRNA expression and is associated with higher CRC risk, indicating an important role in CRC genetic susceptibility.
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