scholarly journals Genetic Variations of CD40 and LTβR Genes Are Associated With Increased Susceptibility and Clinical Outcome of Non-Small-Cell Carcinoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Foteinos-Ioannis D. Dimitrakopoulos ◽  
Anna G. Antonacopoulou ◽  
Anastasia E. Kottorou ◽  
Melpomeni Kalofonou ◽  
Nikolaos Panagopoulos ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Clinical Outcome ◽  
Tumor Necrosis ◽  
Disease Risk ◽  
Tumor Necrosis Factor Receptor ◽  
Small Cell ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Nsclc Patients ◽  
Necrosis Factor

BackgroundImmune system-related receptors CD40 (tumor necrosis factor receptor superfamily member 5), BAFFR (tumor necrosis factor receptor superfamily member 13C), and LTβR (tumor necrosis factor receptor superfamily member 3) play a pivotal role in non-small-cell lung cancer (NSCLC). To further evaluate their role in NSCLC, CD40 rs1883832 (T>C), BAFFR rs7290134 (A>G), and LTβR rs10849448 (A>G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.MethodsThe three selected SNPs were evaluated in 229 NSCLC patients and 299 healthy controls, while CD40, BAFFR, and LTβR protein expression was assessed by immunohistochemistry in 96 tumor specimens from NSCLC patients.ResultsIn total, CD40 rs1883832 was associated with NSCLC risk, with the T allele, after adjusting for cofactors, being related to increased risk (p = 0.007; OR 1.701). Moreover, the CT genotype was associated with increased risk (p = 0.024; OR 1.606) and poorer 5-year overall survival (OS) after adjusting for cofactors (p = 0.001, HR 1.829), while CC was associated with higher CD40 expression in tumorous cells (p = 0.040) and in stromal cells (p = 0.036). In addition, AA homozygotes for the LTβR rs10849448 had increased risk for NSCLC in multivariate analysis (p = 0.008; OR, 2.106) and higher LTβR membranous expression (p = 0.035). Although BAFFR rs7290134 was associated with BAFFR membranous expression (p = 0.039), BAFFR rs7290134 was not associated with neither the disease risk nor the prognosis of NSCLC patients.ConclusionsIn conclusion, CD40 rs1883832 and LTβR rs10849448 seem to be associated with increased risk for NSCLC, while CD40 rs1883832 is also associated with OS of patients with NSCLC.

scholarly journals Tumor necrosis factor receptor 1 functions as a tumor suppressor

2012 ◽  
Vol 302 (2) ◽  
pp. G195-G206 ◽  
Author(s):  
Fengqi Chang ◽  
Michelle R. Lacey ◽  
Mostafa Bouljihad ◽  
Kerstin Höner zu Bentrup ◽  
Ilana S. Fortgang
Keyword(s):  
Weight Loss ◽  
Tumor Necrosis Factor ◽  
Tumor Suppressor ◽  
Tumor Necrosis ◽  
Severe Disease ◽  
Tumor Necrosis Factor Receptor ◽  
Experimental Colitis ◽  
Epithelial Proliferation ◽  
Increased Risk ◽  
Necrosis Factor

Tumor necrosis factor (TNF) is a key player in inflammatory bowel disease and has been variably associated with carcinogenesis, but details of the cross talk between inflammatory and tumorigenic pathways remain incompletely understood. It has been shown that, in C57BL/6 mice, signaling via TNF receptor 1 (TNFR1) is protective from injury and inflammation in experimental colitis. Therefore, we hypothesized that loss of TNFR1 signaling would confer increased risk of developing colitis-associated carcinoma. Using three models of murine tumorigenesis based on repeated bouts of inflammation or systemic tumor initiator, we sought to determine the roles of TNF and TNFR1 with regard to neoplastic transformation in the colon in wild-type (WT), TNFR1 knockout (R1KO), and TNF knockout (TNFKO) mice. We found R1KO animals to have more severe disease, as defined by weight loss, hematochezia, and histology. TNFKO mice demonstrated less weight loss but were consistently smaller, and rates and duration of hematochezia were comparable to WT mice. Histological inflammation scores were higher and neoplastic lesions occurred more frequently and earlier in R1KO mice. Apoptosis is not affected in R1KO mice although epithelial proliferation following injury is more ardent even before tumorigenesis is apparent. Lastly, there is earlier and more intense expression of activated β-catenin in these mice, implying a connection between TNFR1 and Wnt signaling. Taken together, these findings show that in the context of colitis-associated carcinogenesis TNFR1 functions as a tumor suppressor, exerting this effect not via apoptosis but by modulating activation of β-catenin and controlling epithelial proliferation.

scholarly journals Association Study of Tumor Necrosis Factor Receptor 1 (TNFR1) Gene Polymorphisms with Schizophrenia in the Polish Population

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Renata Suchanek-Raif ◽  
Krzysztof Kucia ◽  
Małgorzata Kowalczyk ◽  
Paweł Raif ◽  
Monika Paul-Samojedny ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Factor Model ◽  
Five Factor Model ◽  
Paranoid Schizophrenia ◽  
Tumor Necrosis Factor Receptor ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Necrosis Factor

Schizophrenia is a devastating mental disorder with undetermined aetiology. Previous research has suggested that dysregulation of proinflammatory cytokines and their receptors plays a role in developing schizophrenia. We examined the association of the three single nucleotide polymorphisms (SNPs; rs4149576, rs4149577, and rs1860545) in the tumor necrosis factor receptor 1 (TNFR1) gene with the development and psychopathology of paranoid schizophrenia in the Polish Caucasian sample consisting of 388 patients and 657 control subjects. The psychopathology was assessed using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). SNPs were genotyped using the TaqMan 5′-exonuclease allelic discrimination assay. The SNPs tested were not associated with a predisposition to paranoid schizophrenia in either the entire sample or after stratification according to gender. However, rs4149577 and rs1860545 SNPs were associated with the intensity of the PANSS excitement symptoms in men, which may contribute to the risk of violent behavior. Polymorphisms in the TNFR1 gene may have an impact on the symptomatology of schizophrenia in men.

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