Dataset Information

Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.

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.

SUBMITTER: Geng P

PROVIDER: S-EPMC4551968 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.

Geng Peiliang P Li Jianjun J Wang Ning N Liao Yunmei Y Ou Juanjuan J Sa Rina R Xie Ganfeng G Liu Chen C Li Hongtao H Xiang Lisha L Liang Houjie H

Scientific reports 20150828

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 (homozyg ...[more]

PMID: 26315998

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Project description:The maintenance of B cell homeostasis requires a tight control of B cell generation, survival, activation, and maturation. In lymphocytes upon activation, increased sensitivity to apoptotic signals helps controlling differentiation and proliferation. The death receptor Fas is important in this context because genetic Fas mutations in humans lead to an autoimmune lymphoproliferative syndrome that is similar to lymphoproliferation observed in Fas-deficient mice. In contrast, the physiological role of TNF-related apoptosis-inducing ligand receptors (TRAIL-Rs) in humans has been poorly studied so far. Indeed, most studies have focused on tumor cell lines and on mouse models whose results are difficult to transpose to primary human B cells. In the present work, the expression of apoptosis-inducing TRAIL-R1 and TRAIL-R2 and of the decoy receptors TRAIL-R3 and TRAIL-R4 was systematically studied in all developmental stages of peripheral B cells isolated from the blood and secondary lymphoid organs. Expression of TRAIL-Rs is modulated along development, with highest levels observed in germinal center B cells. In addition, T-dependent and T-independent signals elicited induction of TRAIL-Rs with distinct kinetics, which differed among B cell subpopulations: switched memory cells rapidly upregulated TRAIL-R1 and -2 upon activation while naïve B cells only reached similar expression levels at later time points in culture. Increased expression of TRAIL-R1 and -2 coincided with a caspase-3-dependent sensitivity to TRAIL-induced apoptosis in activated B cells but not in freshly isolated resting B cells. Finally, both TRAIL-R1 and TRAIL-R2 could signal actively and both contributed to TRAIL-induced apoptosis. In conclusion, this study provides a systematic analysis of the expression of TRAIL-Rs in human primary B cells and of their capacity to signal and induce apoptosis. This dataset forms a basis to further study and understand the dysregulation of TRAIL-Rs and TRAIL expression observed in autoimmune diseases. Additionally, it will be important to foresee potential bystander immunomodulation when TRAIL-R agonists are used in cancer treatment.

Project description:STUDY DESIGN:Meta-analysis to collect all the relevant studies to further investigate whether or not the FAS ligand (FASL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genetic polymorphisms are associated with susceptibility to intervertebral disc degeneration (IDD) in Chinese Han population. OBJECTIVE:To investigate whether or not the FASL and TRAIL genetic polymorphisms are associated with susceptibility to IDD in Chinese Han population. SUMMARY OF BACKGROUND DATA:FASL and TRAIL are both apoptotic gene. Several studies have assessed the associations of FASL and TRAIL gene with risk of IDD in Chinese Han population, but the results are inconsistent. METHODS:We systematically searched the PubMed, EMBASE, Medline, Scopus, Web of Science, CBM, and the Cochrane Library databases. Eligible studies assessing the polymorphisms in the FASL and TRAIL gene and risk of IDD were incorporated. The pooled odds ratio (OR) with its 95% confidence intervals (95% CI) was used. RESULTS:Six studies with a total of 1766 IDD cases and 1533 controls were finally included in the meta-analysis. Meta-analysis of FASL-844C/T (rs763110) polymorphism was statistically associated with decreased IDD risk under all genetic models (allele model: OR?=?0.68, 95% CI 0.59-0.80, P?=?0.000; homozygote model: OR?=?0.35, 95% CI 0.25-0.53, P?=?0.000; dominant model: OR?=?0.38, 95% CI 0.25-0.58, P?=?0.000; recessive model: OR?=?0.69, 95% CI 0.58-0.84, P?=?0.000). There was a significant association between TRAIL-1595C/T (rs1131580) polymorphism with increased IDD risk under each genetic model (allele model: OR?=?1.77, 95% CI 1.47-2.13, P?=?0.000; homozygote model: OR?=?2.44, 95% CI 1.70-3.51, P?=?0.000; dominant model: OR?=?1.67, 95% CI 1.22-2.29, P?=?0.002; recessive model: OR?=?3.13, 95% CI 2.40-4.08, P?=?0.000). In addition, the association between TRAIL-1525G/A (rs1131568) polymorphism and the susceptibility of IDD was statistically significant under all genetic models. CONCLUSION:The present meta-analysis demonstrated that FASL and TRAIL polymorphisms were significantly associated with susceptibility to IDD in Chinese Han population. LEVEL OF EVIDENCE:1.

Dataset Information

Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.

Publications

Genetic association between TRAIL-R1 Thr209Arg and cancer susceptibility.

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