Fu Qiang, Zhang Guoqiang, Chen Hongwei, Zheng Youwei, Cheng Jing
General Surgery Department, Tumor Hospital Affiliated Hospital of Zhengzhou University Henan Tumor Hospital, Zhengzhou, Henan, 450000, China.
Tumour Biol. 2013 Dec;34(6):3721-9. doi: 10.1007/s13277-013-0956-z. Epub 2013 Aug 3.
It has been demonstrated that MDM2 is a well-established negative regulator of the p53 protein and might be associated with a significantly earlier age of onset of several tumors, including colorectal cancer (CRC). In recent years, a T to G substitution (SNP309) in the promoter of MDM2 has been extensively studied as a potential CRC risk factor; however, the results are inconsistent. To derive a more precise estimation of association between MDM2 SNP309 polymorphism and CRC risk, we conducted a meta-analysis of 11 studies with 4,050 CRC cases and 3,688 controls. For MDM2 SNP309 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, source of controls, and Hardy-Weinberg equilibrium (HWE) in controls, a significantly increased risk was observed among Asians (heterozygous model: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.06-1.39, P = 0.005), population-based studies (heterozygous model: OR = 1.17, 95% CI = 1.02-1.34, P = 0.027), and among studies without the HWE (recessive model: OR = 1.42, 95% CI = 1.03-1.94, P = 0.030). When excluding three studies deviated from HWE, the significant results were also observed for heterozygous model in overall population (OR = 1.16, 95% CI = 1.02-1.31, P = 0.020). No publication bias was found in the present study. In conclusion, this meta-analysis suggests that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on CRC.
已有研究表明，MDM2是一种成熟的p53蛋白负调控因子，可能与包括结直肠癌（CRC）在内的多种肿瘤发病年龄显著提前有关。近年来，MDM2启动子中的T到G替换（SNP309）作为潜在的CRC风险因素受到广泛研究；然而，结果并不一致。为了更精确地估计MDM2 SNP309多态性与CRC风险之间的关联，我们对11项研究进行了荟萃分析，这些研究包括4050例CRC病例和3688例对照。对于MDM2 SNP309多态性，当将所有研究纳入荟萃分析时，在所有遗传模型中均未发现明显关联。在按种族、对照来源以及对照中的哈迪-温伯格平衡（HWE）进行的亚组分析中，在亚洲人群（杂合子模型：比值比（OR）=1.21，95%置信区间（CI）=1.06 - 1.39，P = 0.005）、基于人群的研究（杂合子模型：OR = 1.17，95% CI = 1.02 - 1.34，P = 0.027）以及未达到HWE的研究（隐性模型：OR = 1.42，95% CI = 1.03 - 1.94，P = 0.030）中观察到风险显著增加。当排除三项偏离HWE的研究时，在总体人群的杂合子模型中也观察到显著结果（OR = 1.16，95% CI = 1.02 - 1.31，P = 0.020）。本研究未发现发表偏倚。总之，这项荟萃分析表明MDM2 SNP309多态性与CRC易感性相关，尤其是在亚洲人群中。需要进一步研究以评估CRC可能存在的基因-基因或基因-环境-生活方式相互作用。
