Abstract
BackgroundThe survivin polymorphisms have been shown to confer genetic susceptibility to various tumors, but the results are inconsistent. In order to accomplish a more precise estimation of the relationship, a meta-analysis was performed.ResultsFor rs9904341, a significantly increased tumor risk was found in overall meta-analysis under C/C vs. G/G (OR = 1.40, 95% CI = 1.13–1.74, p = 0.002), dominant (OR = 1.18, 95% CI = 1.01–1.38, p = 0.039) and recessive (OR = 1.34, 95% CI = 1.13–1.58, p = 0.001) genetic models and Asians group. In subgroup analyses of tumor types, we found a significant association between this SNP and an increased risk of gastric, colorectal, bladder and other tumors as well as a decreased risk of hepatocellular cancer. For rs17878467, a significantly decreased tumor risk was identified in overall meta-analysis for allele contrast (T vs. C: OR = 0.69, 95% CI = 0.51–0.92, p = 0.012), C/T vs. C/C (OR = 0.61, 95% CI = 0.42–0.88, p = 0.009) and dominant (OR = 0.62, 95% CI = 0.43–0.88, p = 0.007) genetic models and Asians group. For rs2071214, we found a significant association between this SNP and an increased tumor risk in overall meta-analysis under G/G vs. A/A (OR = 1.51, 95% CI = 1.04–2.18, p = 0.029) and recessive (OR = 1.54, 95% CI = 1.07–2.22, p = 0.020) genetic models and Asians group. Besides, there was a significant association of rs8073069 with an increased tumor risk under recessive genetic model (OR = 1.37, 95% CI = 1.01–1.84, p = 0.040), while no significant association between rs1042489 and tumor risk was detected.ConclusionsThe survivin rs9904341 most likely contributed to increased susceptibility to tumor in Asians as well as to gastric, colorectal and bladder cancers. As for rs17878467, the T allele might be a protective factor for tumor, especially in Asians. Moreover, the survivin rs8073069 and rs2071214 seemed to be associated with an increased tumor risk in Asians, while there was no association between the survivin rs1042489 and tumor risk.
Highlights
Apoptosis, known as programmed cell death, plays an important role in the development and maintenance of tissue homeostasis in multicellular organisms [1,2]
In the stratified analysis by ethnicity, we found a significant association of this single nucleotide polymorphism (SNP) with an increased tumor risk in Asians under C/C vs. G/G (OR = 1.52, 95% confidence intervals (CIs) = 1.19–1.95, p = 0.001), dominant (OR = 1.25, 95% CI = 1.06–1.47, p = 0.006) and recessive (OR = 1.40, 95% CI = 1.16–1.70, p = 0.001) genetic models; no evidence of associations was detected in Caucasian and mixed populations (Table 2)
For the survivin rs2071214 (Table 2, Figure 4A), we found a significant association between this SNP and an increased tumor risk under G/G vs. A/A (OR = 1.51, 95% CI = 1.04–2.18, p = 0.029) and recessive (OR = 1.54, 95% CI = 1.07–2.22, p = 0.020) genetic models
Summary
Known as programmed cell death, plays an important role in the development and maintenance of tissue homeostasis in multicellular organisms [1,2]. Previous evidences have indicated that survivin can block a common downstream part of two major apoptosis pathways, the extrinsic or receptor-mediated pathway and the intrinsic or mitochondrial pathway, through directly and/or indirectly inhibiting initiator (caspase-9) and effector caspases (caspase-3 and -7), and preventing apoptosis [9]. Increased level of survivin expression has been found in various malignancies, including gastric, colorectal and other tumors [10,11,12,13], suggesting that survivin may play a critical role in tumorigenesis, with important biological, prognostic and therapeutic implications. In order to accomplish a more precise estimation of the relationship, a meta-analysis was performed
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