Abstract
We aimed to determine the indecisive association between tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) Thr209Arg polymorphism and inherited susceptibility to cancer. A meta-analysis combining data on 9,517 individuals was performed to assess the association between TRAIL-R1 Thr209Arg and cancer incidence. The summary ORs with 95% CI calculated with the fixed effects model suggested that Thr209Arg was not significantly associated with cancer susceptibility (homozygous model: OR 0.98, 95% CI 0.88–1.09; heterozygous model: OR 0.95, 95% CI 0.87–1.04; allele frequency model: OR 0.99, 95% CI 0.94–1.05; dominant model: OR 0.98, 95% CI 0.91–1.05; recessive model: OR 1.01, 95% CI 0.92–1.10). Stratified analysis by ethnicity and cancer type yielded similar null associations. These statistical data suggest that Thr209Arg in exon 4 of the TRAIL-R1 gene may not represent a modifier of susceptibility to cancer.
Highlights
Among the various genomic abnormalities, allelic loss at human chromosome 8p21 is frequent in all kinds of cancer and has received widespread attention in recent years[1,2]
Resistance to apoptosis destroys the balance between cell death and growth, facilitating tumorigenesis
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-R1 is a transmembrane protein with a death domain essential for apoptotic regulation
Summary
Among the various genomic abnormalities, allelic loss at human chromosome 8p21 is frequent in all kinds of cancer and has received widespread attention in recent years[1,2]. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a homotrimeric cytokine located at chromosome band 8p21. TRAIL-R1 enables cell death and triggers apoptotic proteases to regulate apoptosis through inducing the oligomerization of intracellular death domains required for the apoptotic signal transduction and forming an extracellular cysteine-rich, ligand-binding domain[6,7,8,9]. There are multiple well-characterized polymorphisms in the TRAIL-R1 gene, but the most extensively studied polymorphism has been the C > G substitution resulting in a threonine to arginine amino acid change in exon 4 (Thr209Arg, rs20575). To determine whether Thr209Arg in the ectodomain of the TRAIL-R1 gene is independently associated with cancer, we conducted a meta-analysis where all usable data identified through several medicine-specific databases have been incorporated
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