Genetic polymorphisms of TP53 (rs1042522) and MDM2 (rs2279744) and colorectal cancer risk: An updated meta-analysis based on 59 case-control studies

Rami M Elshazli; Eman A Toraih; Abdelaziz Elgaml; Emad Kandil; Manal S Fawzy

doi:10.1016/j.gene.2020.144391

Genetic polymorphisms of TP53 (rs1042522) and MDM2 (rs2279744) and colorectal cancer risk: An updated meta-analysis based on 59 case-control studies

Gene. 2020 Apr 15:734:144391. doi: 10.1016/j.gene.2020.144391. Epub 2020 Jan 27.

Authors

Rami M Elshazli¹, Eman A Toraih², Abdelaziz Elgaml³, Emad Kandil⁴, Manal S Fawzy⁵

Affiliations

¹ Department of Biochemistry and Molecular Genetics, Faculty of Physical Therapy, Horus University - Egypt, New Damietta, Egypt. Electronic address: Relshazly@horus.edu.eg.
² 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.
³ Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University - Egypt, New Damietta, Egypt.
⁴ Division of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.

PMID: 32001373
DOI: 10.1016/j.gene.2020.144391

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.

Keywords: Colorectal cancer; MDM2; Meta-analysis; TP53; Variants.

Publication types

Meta-Analysis
Review

MeSH terms

Colorectal Neoplasms / genetics*
Genetic Predisposition to Disease
Humans
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-mdm2 / genetics*
Tumor Suppressor Protein p53 / genetics*

Substances

TP53 protein, human
Tumor Suppressor Protein p53
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2