Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

• Main Authors: Xie LG, Sun Y, Chen T, Tian DW, Li YJ, Zhang Y, Ding N, Shen ZH, Xu H, Nian XW, Sha N, Han RF, Hu HL, Wu CL
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-12-01
• Series: OncoTargets and Therapy
• Subjects: bladder cancer; MDM2; single nucleotide polymorphism; rs2279744; recurrence; mate-analysis
• Online Access: https://www.dovepress.com/association-between-mdm2-snp309-tgtg-polymorphism-and-the-risk-of-blad-peer-reviewed-article-OTT

Linguo Xie,1,2,* Yan Sun,2,* Tao Chen,1,2,* Dawei Tian,1,2 Yujuan Li,3 Yu Zhang,1,2 Na Ding,2 Zhonghua Shen,1,2 Hao Xu,1,2 Xuewu Nian,4 Nan Sha,1,2 Ruifa Han,1,2 Hailong Hu,1,2 Changli Wu1,2 Objective: Human murine double minute 2 protein (MDM2) is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05). In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881), and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05). The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05), and no association was observed in total populations and Asians (P>0.05). Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but this single nucleotide polymorphism may be associated with genetic susceptibility of bladder cancer among Caucasians. Keywords: bladder cancer, MDM2, single nucleotide polymorphism, rs2279744, recurrence, meta-analysis