Abstract
Death receptor 4 (TRAIL-R1 or DR4) polymorphisms have been associated with cancer risk, but findings have been inconsistent. To estimate the relationship in detail, a meta-analysis was here performed. A search of PubMed was conducted to investigate the association between DR4 C626G, A683C and A1322G polymorphisms and cancer risk, using odds ratios (ORs) with 95% confidence intervals. The results suggested that DR4 C626G and A683C polymorphisms were indeed associated with cancer risk (for C626G, dominant model, OR 0.991, 95%CI 0.866-1.133, p=0.015; for A683C, additive model, OR=1.140, 95%CI: 0.948-1.370, p=0.028; dominant model, OR=1.156, 95%CI: 0.950-1.406, p=0.080) in the Caucasian subgroup. However, the association was not significant between DR4 polymorphism A1322G with cancer risk in Caucasians (For A1322G, additive model: OR 1.085, 95%CI 0.931-1.289, p=0.217; dominant model: OR 1.379, 95%CI 0.934-2.035, p=0.311; recessive model: OR 1.026, 95%CI 0.831-1.268 p=0.429.). In summary, our finding suggests that DR4 polymorphism C626G and A683 rather than A1322G are associated with cancer risk in Caucasians.
Highlights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a new member of the TNF superfamily, is a transmembrane protein which can selectively kill cancer cells but not normal cells, making it an attractive agent for cancer therapy (Yagita et al, 2004)
The results suggested that Death receptor 4 (DR4) C626G and A683C polymorphisms were associated with cancer risk in the Caucasian subgroup
Our finding suggests that DR4 polymorphism C626G and A683 rather than A1322G are associated with cancer risk in Caucasians
Summary
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a new member of the TNF superfamily, is a transmembrane protein which can selectively kill cancer cells but not normal cells, making it an attractive agent for cancer therapy (Yagita et al, 2004). TRAIL induces apoptosis by binding to DR4 and DR5 and subsequent activation of the apoptotic cascade through caspase-8 and Fas-associating death domain (FADD), forming the death inducing death-inducing signaling complex (DISC), leading to activation of the executioner caspases and causing cell death (MacFarlane et al, 1997; Pan et al, 1997; Sprick et al, 2000). DR4 consists of two extracellular cysteine-rich, ligand-binding pseudorepeats (50s and 90s loops), one single transmembrane helix as well as the apoptosis-triggering cytoplasmic death domain (Hengartner et al, 2000; Evan et al, 2001; Koornstra et al, 2003; Bouralexis et al, 2005). The C626G in the ectodomain region of DR4, whereas A683C in extracellular cycteine-rich domain and A1322G in the death domain of DR4 (Chen et al, 2009)
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