Association between Laryngeal Squamous Cell Carcinoma and Polymorphisms in Tumor Necrosis Factor Related Apoptosis Induce Ligand (TRAIL), TRAIL Receptor and sTRAIL Levels

Abstract

The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

TRAIL and TRAIL Receptors as Prognostic Markers in Breast Cancer Patients

“…These findings suggest that decreased TRAIL may allow cancer cells to escape immune surveillance and apoptosis [14]. Verim A also indicated a statistically significant association between TRAIL, and clinical parameters including stage, lymph node, metastasis, perineural invasion and degree of tumor differentiation in Lx SCC patients [32].…”

Modulators of Redox Metabolism in Head and Neck Cancer

“…The role of 1-C/folate metabolism in maintaining the reduced NADPH pool has been reported in several publications (102,289). Relationships between polymorphisms in folate metabolism enzymes (e.g., methylenetetrahydrofolate reductase [MTHFR], serine hydroxymethyltransferase [SHMT]), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and immune response factors (e.g., interleukin [IL]-8, toll-like receptor 10 [TLR10]), and HNSCC risks have been investigated (115,218,246,304). However, the number of such studies is limited, and it is difficult to draw definite conclusions.…”

Construction and Analysis of Protein-Protein Interaction Network to Identify the Molecular Mechanism in Laryngeal Cancer

“…This biological process is involved in cancer development and progression and is regulated via activation of tumor necrosis factor receptor super-family (TNFRSF) by tumor necrosis factor related apoptosis induce ligand (TRAIL). Several papers have studied the different levels of TRAIL and TRAIL receptor in laryngeal cancer (Verim et al 2014;Yoldas et al 2011). TRAIL is known as a key effector molecule in cell signalling pathway that would trigger apoptosis in cancer cells.…”