Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Wuxi, P.R. China.
DNA Cell Biol. 2012 Mar;31(3):355-9. doi: 10.1089/dna.2011.1338. Epub 2011 Jul 19.
MDM2 is a phosphoprotein that interacts with p53 and inhibits its activity. Recently, a T to G substitution (SNP309) in the promoter of MDM2 was identified and associated with increased MDM2 expression and a significantly earlier age of onset of several tumors, including colorectal cancer. Several studies evaluated the association between SNP309 and colorectal cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of association between MDM2 SNP309 and risk of colorectal cancer, we performed a meta-analysis of 3347 colorectal cancer cases and 3102 controls from eight published case-control studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. The results suggested that the variant genotype was associated with a significantly increased colorectal cancer risk (GT vs. TT: OR=1.19, 95% CI=1.06-1.35; p=0.005). In the stratified analyses, significantly increased risks were found among Asian populations (OR=1.28, 95% CI=1.10-1.50; p=0.002) and population-based studies (OR=1.18, 95% CI=1.03-1.34; p=0.016). Although some bias could not be eliminated, this meta-analysis suggested that the MDM2 SNP309 polymorphism is a low-penetrance risk factor for the development of colorectal cancer, particularly among Asians.
MDM2 是一种与 p53 相互作用并抑制其活性的磷酸化蛋白。最近，在 MDM2 的启动子中发现了 T 到 G 的取代（SNP309），并与 MDM2 表达的增加以及包括结直肠癌在内的几种肿瘤的发病年龄明显提前有关。几项研究评估了 SNP309 与不同人群结直肠癌风险之间的关联。然而，结果仍然存在争议，而不是结论性的。为了更准确地评估 MDM2 SNP309 与结直肠癌风险之间的关联，我们对来自 8 项已发表的病例对照研究的 3347 例结直肠癌病例和 3102 例对照进行了荟萃分析。我们使用比值比（ORs）及其 95％置信区间（CIs）来评估关联的强度。结果表明，变异基因型与结直肠癌风险显著增加相关（GT 与 TT：OR=1.19，95％CI=1.06-1.35；p=0.005）。在分层分析中，在亚洲人群（OR=1.28，95％CI=1.10-1.50；p=0.002）和基于人群的研究中（OR=1.18，95％CI=1.03-1.34；p=0.016）发现了明显增加的风险。尽管不能消除一些偏倚，但这项荟萃分析表明，MDM2 SNP309 多态性是结直肠癌发生的低外显率风险因素，尤其是在亚洲人群中。
