The State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.
Arch Med Res. 2011 Feb;42(2):149-55. doi: 10.1016/j.arcmed.2011.02.002.
The murine double minute 2 (MDM2) gene encodes a negative regulator of the tumor protein p53. A single nucleotide polymorphism (SNP) in MDM2 promoter, SNP309 T>G, has been reported to alter MDM2 protein expression and accelerate tumor formation in humans. Studies investigating the association between the polymorphism and human hepatocellular carcinoma (HCC) risk reported conflicting results. We performed a meta-analysis to explore the association of this polymorphism and HCC risk.
All eligible studies published were searched for in PubMed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for the association using fixed- and random-effects models.
We identified five case-control studies including 738 cases and 1014 controls for the present meta-analysis. In studies with limited data, we detected significant associations for all genetic models in the overall analysis (OR = 2.51, 95% CI = 1.88-3.36 for GG vs. TT, p <0.001, P(het) = 0.666; OR = 1.71, 95% CI = 1.35-2.18 for TG vs. TT, p <0.001, P(het) = 0.925; OR = 1.94, 95% CI = 1.54-2.43 for dominant model TG + GG vs. TT, p <0.001, P(het) = 0.772; OR = 1.74, 95% CI = 1.39-2.20 for recessive model GG vs. TT + TG, p <0.001, P(het) = 0.656). Moreover, in the subgroup analysis based on Hardy-Weinberg equilibrium (HWE) in controls, sample size, and ethnicity, significant associations were observed in most genetic models.
This meta-analysis suggests that the MDM2 309 G allele probably acts as an important HCC risk factor. To further confirm our findings, well-designed studies with large sample sizes and representing different ethnicities are required.
鼠双微体 2（MDM2）基因编码肿瘤蛋白 p53 的负调控因子。已报道 MDM2 启动子中的单核苷酸多态性（SNP）SNP309T>G 改变 MDM2 蛋白表达并加速人类肿瘤形成。研究该多态性与人类肝细胞癌（HCC）风险之间的关联的研究报告结果相互矛盾。我们进行了荟萃分析以探讨该多态性与 HCC 风险的关联。
在 PubMed 中搜索所有已发表的符合条件的研究。使用固定效应模型和随机效应模型评估关联的粗比值比（OR）和 95％置信区间（CI）。
我们确定了五项病例对照研究，其中包括 738 例病例和 1014 例对照，进行了本次荟萃分析。在数据有限的研究中，我们在总体分析中检测到所有遗传模型均有显著关联（OR=2.51，95％CI=1.88-3.36，GG 与 TT 相比，p<0.001，P(het)=0.666；OR=1.71，95％CI=1.35-2.18，TG 与 TT 相比，p<0.001，P(het)=0.925；OR=1.94，95％CI=1.54-2.43，显性模型 TG+GG 与 TT 相比，p<0.001，P(het)=0.772；OR=1.74，95％CI=1.39-2.20，隐性模型 GG 与 TT+TG 相比，p<0.001，P(het)=0.656）。此外，在基于对照组 Hardy-Weinberg 平衡（HWE）、样本量和种族的亚组分析中，大多数遗传模型均观察到显著关联。
本荟萃分析表明，MDM2 309G 等位基因可能是 HCC 的重要危险因素。为了进一步证实我们的发现，需要设计良好的、具有较大样本量和代表不同种族的研究。
