Objective To investigate the association between MDM2 gene promoter SNP 309 polymorphism and leukemia susceptibility. Methods Such databases as Ovid, EBSCO, PubMed, CNKI, CBM, VIP and WanFang Data were searched to collect the case-control studies published from January 1990 to June 2012. According to the inclusion and exclusion criteria, the studies were screened, the data were extracted, and the methodological quality of the included studies was evaluated. Then meta-analysis was conducted using RevMan 5.0 and Stata 10.0 software, the pooled odds ratio (ORs) with 95% confidence interval (CI) were calculated, and the sensitivity and publication bias were evaluated at the same time. Results A total of 9 studies within 8 articles were included, which involved 1 821 cases and 5 642 controls. The results of meta-analysis showed that, the susceptibility of leukemia was increased in the G allele carriers compared with the T allele carriers (OR=1.26, 95%CI 1.08 to 1.46, P=0.003), and the leukemia risk was higher in the GG genotype populations compared with the TT genotype populations (OR=1.46, 95%CI 1.02 to 2.10, P=0.04). Among Asians with recessive models, the leukemia risk was higher in the homozygous GG genotype compared with both the heterozygous GT genotype and the homozygous TT genotype (OR=2.00, 95%CI 1.37 to 2.92, P=0.000 3). There was no obvious publication bias. Conclusion MDM2 gene promoter SNP 309 polymorphism is associated with the susceptibility of leukemia, and the G allele is likely to be the risk factor for leukemia.
Objective To investigate the correlation between MDM2 SNP309 and gastric cancer (GC) risk in Eastern Asian population. Methods Two reviewers independently searched MEDLINE, EMbase and CBM (from January 1st, 1990 to October 23rd, 2012) for case-control studies on the correlation between MDM2 SNP309 and GC risk in Eastern Asian population. Two reviewers independently screen literature, extracted the data, and assessed the methodological quality. Then meta-analysis was performed using RevMan 5.0 software. Results 5 case-control studies were finally included involving 1 621 GC cases and 2 639 controls. The pooled results showed that the variant homozygote (309GG genotype) was significantly associated with an increased risk of GC as compared to wild-type homozygote (309TT genotype: OR=1.54, 95% CI 1.04 to 2.29, P=0.02). Nevertheless, no association was found in comparison of variant heterozygote (309TG genotype) between wild-homozygote (309TT genotype: OR=1.03, 95% CI 0.75 to 1.42, P=0.006). A significantly increased risk of GC was observed for the recessive model (GG vs. TT/TG: OR=1.49, 95% CI 1.20 to 1.84, P=0.07). While in the dominant model (GG/TG vs. TT), non-significant association was observed (OR=1.18, 95% CI 0.84 to 1.65, P=0.001). Conclusion The MDM2 309GG may be significantly associated with an increased risk of GC among Eastern Asians.
A series of novel polycyclic spiro-fused carbocyclicoxindoles were synthesized and investigated for their in vitro antiproliferative activities against nine human cancer cell lines. Five compounds (10i, 101, 10n, 10p, and 10r) demonstrated anticancer activities against A2780s cells with IC50 values of less than 30 mu M. In particular, compound 10i showed anticancer activities against seven cancer cell lines and stronger activities than cisplatin in A2780s, A2780T, L126, and HCT116 cells. Further studies illustrated that compound 101 arrested cell cycle in G1 phase and induced apoptosis of HCT116 cells. This compound also effectively increased the protein levels of cleaved caspase-3, p53, and MDM2. Molecular docking results revealed that compound 101 could bind well to the p53-binding site on MDM2, indicating that it might work by blocking the MDM2-p53 interactions. (C) 2016 Elsevier Masson SAS. All rights reserved.
ObjectiveTo systematically review the relationship between T309G polymorphism of murine double minute 2 (MDM2) gene and susceptibility of prostate cancer. MethodsThe PubMed, Embase, WanFang Data, CNKI databases were electronically searched to collect case-control studies related to the objects from inception to May, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 14.0 software. ResultsA total of 10 studies involving 5 781 patients and 5 477 healthy controls were included. The results of meta-analysis showed that, the MDM2 gene T309G polymorphism was not associated with preeclampsia (allele model G vs. T: OR=0.89, 95%CI 0.77 to 1.04, P=0.13; homozygote model GG vs. TT: OR=0.86, 95%CI 0.64 to 1.16, P=0.32; heterozygote model TG vs. TT: OR=1.04, 95%CI 0.86 to 1.26, P=0.12; dominant model GG+TG vs. TT: OR=0.96, 95%CI 0.89 to 1.04, P=0.36; recessive model GG vs. TG+TT: OR=0.84, 95%CI 0.63 to 1.14, P=0.27). The results of subgroup analysis based on ethnicity and source of control were similar to the overall results. Sensitivity analysis showed that the results were robust. Conclusion Current evidence shows that the MDM2 gene T309G polymorphism was not associated with prostate cancer susceptibility. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.