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.
Highlights
Larynx cancer is a multifactorial disease that environmental and genetic factors play role in its etiology and has high incidence among the types of head and neck cancers
DR4 C626G and Tumor necrosis factor related apoptosis induce ligand (TRAIL) 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and soluble TRAIL (sTRAIL) levels were measured by ELISA
We aimed to investigate the polymorphisms of DR4 C626G and TRAIL 1595 C/T and sTRAIL levels and possible effects of these parameters on laryngeal carcinoma susceptibility or progression
Summary
Larynx cancer is a multifactorial disease that environmental and genetic factors play role in its etiology and has high incidence among the types of head and neck cancers. Papilloma virus infection, and exposure to toxic substances are other risk factors for larynx cancer. In addition to environmental factors, accumulation of many mutations may alter the balance between cell proliferation and apoptosis, and may lead to development of cancer (Manjarrez et al, 2006; Braakhuis et al, 2012). Extrinsic pathway of apoptosis in cells triggers by tumor necrosis factor (TNF)related apoptosis-inducing factor (TRAIL) which is a key effector molecule of cellular signal mechanism (Wang, 2008). There is a rapidly increasing evidence that substantiates the fact that TRAIL induced apoptosis in cancer cells through death receptors (DR4 and DR5). TRAIL is capable of binding to four transmembrane receptors out of the soluble receptor which is called as osteoprogenator.
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