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 occurringin 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 laryngealcarcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAILand TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patientswith laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/Tgenotypes 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 ofDR4 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 genotypein patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significantrelationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels inthe laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patientswith early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might beassociated with progression of laryngeal cancer in the Turkish population.

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