Characteristics of studies
For the process of selection, as evident from Figure 1, an aggregate of 300 research works was retrieved on the preliminary literature search, associated with the correlation existing between CTLA-4 +49G/A genetic polymorphism and malignant bone tumors susceptibility. Subsequent to removing the duplicated articles, after the scanning of the titles as well as the abstracts of these research works, with an aggregate of 50 research works remained. Thereafter, we carried out the evaluation of the full-text, together with excluding the ineligible studies; also, 6 case-control research works, having an aggregate of 2609 participants, were counted on in the present meta-analysis6, 18-22. The key features of the included research works are demonstrated in Table 1.
Association of CTLA-4 +49G/A polymorphism with malignant bone tumor risk
6 research works, having an aggregate of 1191 patients as well as 1418 controls, were counted on in the present meta-analysis in order to evaluate the correlation of the CTLA-4 +49G/A genetic polymorphisms with the susceptibility to malignant bone tumors. In addition, any considerable heterogeneity was not observed to exist between these research works (I2=0, P = 0.996), indicating that these studies were homogeneous, and thereby the use of the fixed-effects model was made for pooling the data (Figure 5). The cumulated findings shed light on the fact that the CTLA-4 +49G/A polymorphism had a significant correlation with an augmented susceptibility to malignant bone tumors subjected to all of the genetic contrast models (A vs. G: OR=1.37, 95%CI=1.22-1.54, P < 0.001; GA vs. GG: OR=1.20, 95%CI=1.01-1.42, P = 0.037; AA vs. GG: OR=2.13, 95%CI=1.63-2.78, P < 0.001; GA+AA vs. GG: OR=1.35, 95%CI=1.15-1.59, P < 0.001; AA vs. GG+GA: OR=2.02, 95%CI=1.60-2.56, P < 0.001) (Figure 2 and Table 2).
In the course of the evaluation of the impact of the CTLA-4 +49G/A polymorphism by source of controls, we discovered significant correlation in both of the population-based populations (A vs. G: OR=1.42, 95%CI=1.16-1.74, P = 0.001; AA vs. GG: OR=1.94, 95%CI=1.22-3.08, P = 0.005; AA vs. GG+GA: OR=2.02, 95%CI=1.39-2.93, P < 0.001) and hospital-based populations (A vs. G: OR=1.35, 95%CI=1.17-1.55, P < 0.001; AA vs. GG: OR=2.23, 95%CI=1.61-3.09, P < 0.001; GA+AA vs. GG: OR=1.33, 95%CI=1.09-1.61, P = 0.004; AA vs. GG+GA: OR=2.03, 95%CI=1.50-2.75, P < 0.001). besides that, no considerable heterogeneity was observed to exist between these research works (I2=0%, P = 0.955) (Figure 5), so, the use of the fixed-effects model was made for pooling the data (Figure 3 and Table 2).
For the purpose of further exploring the correlation of the CTLA-4 +49G/A genetic polymorphisms with the susceptibility to the malignant bone tumors, we carried out the subgroup analysis in accordance with the type of cancer. With regard to osteosarcoma, there were four research works that had an aggregate of 660 patients as well as 754 controls, and no significant heterogeneity between these studies was found (I2=0%, P = 0.960) (Figure 5). That was why the use of the fixed-effects model was made for pooling the data. The cumulated findings indicate that the CTLA-4 +49G/A polymorphism had a significant correlation with an augmented susceptibility to osteosarcoma (A vs. G: OR=1.38, 95%CI=1.18-1.61, P < 0.001; AA vs. GG: OR=2.04, 95%CI=1.42-2.93, P < 0.001; GA+AA vs. GG: OR=1.34, 95%CI=1.07-1.68, P = 0.012; AA vs. GG+GA: OR=2.04, 95%CI=1.50-2.77, P < 0.001). With regard to Ewing’s sarcoma, the pooled results also shed light on the fact that the CTLA-4 +49G/A polymorphism had a considerable correlation with an increased the susceptibility to Ewing’s sarcoma (Figure 4 and Table 2).
Publication bias and sensitivity analysis
As evident from Figure 6, the funnel plots appeared as approximately symmetrical, and the findings from Egger’s test also extended support to the symmetry. The results suggested that the possible publication bias could be excluded. The sensitivity analysis suggested that our results were statistically robust as well as credible while omitting the studies one following the other.