Abstract
Objective: 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.
Methodology: 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.
Results: 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.
Conclusion: TP53 (rs1042522) and MDM2 (rs2279744) variants might represent candidate risk factors for CRC susceptibility.