Department of Biochemistry and Molecular Genetics, Faculty of Physical Therapy, Horus University - Egypt, New Damietta, Egypt.
Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; Genetics unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Egypt.
Gene. 2020 Apr 15;734:144391. doi: 10.1016/j.gene.2020.144391. Epub 2020 Jan 27.
Several earlier reports implicated TP53 (rs1042522) and MDM2 (rs2279744) variants in outcome of colorectal cancer (CRC), but with inconclusive findings. This current meta-analysis designed to uncover the role of these variants in CRC risk.
Two independent investigators extracted 59 eligible case-control studies from different electronic databases involving Scopus, Web of Science and PubMed prior to June 2019. Pooled odds ratios (ORs) and "95% confidence intervals (CIs)" were computed for different hereditary models. Stratification and heterogeneity analyses, and "Begg's funnel plots" were conducted. In silico data analyses of the functional and structural properties of the study variants were applied.
In general, 47 and 16 case-control reports for TP53 (11,589 patients and 13,622 controls) and MDM2 (6841 CRC patients and 8792 healthy controls), respectively were enrolled in this meta-analysis. A significant association of TP53 (rs1042522) variant with increased CRC risk in overall pooled subjects under recessive model [(CC vs. GC + GG, OR = 1.134, 95% CI = 1.006-1.278, P = 0.039)] was observed. Moreover, an evidence of MDM2 (rs2279744) association with increased CRC risk in overall pooled subjects under dominant and heterozygote models [(TG + GG vs. TT, OR = 1.120, 95% CI = 1.003-1.250, P = 0.044) and (TG vs. TT, OR = 1.189, 95% CI = 1.076-1.313, P = 0.001), respectively] was reported. Additionally, TP53 (rs1042522) and MDM2 (rs2279744) showed an association with CRC risk among Asians and Africans under a recessive model, and among Asians under different genetic models, respectively, by stratification analysis.
TP53 (rs1042522) and MDM2 (rs2279744) variants might represent candidate risk factors for CRC susceptibility.
先前有几项报告表明 TP53(rs1042522)和 MDM2(rs2279744)变异与结直肠癌(CRC)的结局有关，但结果尚无定论。本研究旨在通过meta 分析来明确这些变异与 CRC 风险的关系。
两名独立研究员从不同的电子数据库（包括 Scopus、Web of Science 和 PubMed）中提取了截至 2019 年 6 月的 59 项符合条件的病例对照研究。使用不同的遗传模型计算了汇总的优势比(ORs)和“95%置信区间(CI)”。进行了分层和异质性分析，并绘制了“Begg 漏斗图”。还对研究变异的功能和结构特性进行了计算机数据分析。
总体而言，这项 meta 分析纳入了 47 项针对 TP53(rs1042522)（11589 例患者和 13622 例对照）和 16 项针对 MDM2(rs2279744)（6841 例 CRC 患者和 8792 例健康对照）的病例对照报告。在总体研究对象中，隐性模型下 TP53(rs1042522)变异与 CRC 风险增加显著相关[(CC 与 GC+GG，OR=1.134，95%CI=1.006-1.278，P=0.039)]。此外，显性和杂合子模型下 MDM2(rs2279744)变异与 CRC 风险增加有关，[(TG+GG 与 TT，OR=1.120，95%CI=1.003-1.250，P=0.044)和(TG 与 TT，OR=1.189，95%CI=1.076-1.313，P=0.001)]。此外，分层分析显示，TP53(rs1042522)和 MDM2(rs2279744)在亚洲人和非洲人中与 CRC 风险呈隐性模型相关，在亚洲人中与不同的遗传模型相关。
TP53(rs1042522)和 MDM2(rs2279744)变异可能是 CRC 易感性的候选危险因素。
