AUTHOR=Zhao Lin , Yin Xiang-Xiongyi , Qin Jun , Wang Wei , He Xiao-Feng 

TITLE=Association Between the TP53 Polymorphisms and Breast Cancer Risk: An Updated Meta-Analysis

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.807466

DOI=10.3389/fgene.2022.807466

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The relationship of <italic>TP53</italic> codons 72, IVS3 16 bp, and IVS6+62A &gt; G polymorphisms with breast cancer (BC) risk has been analyzed in seventeen published meta-analyses. However, the credibility of statistically significant associations was ignored and many new studies have been reported on these themes.</p><p><bold>Objectives:</bold> To explore whether <italic>TP53</italic> codons 72, IVS3 16 bp, and IVS6+62A &gt; G polymorphisms are associated with BC risk and the clinical phenomena.</p><p><bold>Methods:</bold> To comprehensively search the data (through October 25, 2021), we provided a clear search strategy and reviewed the references of published meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used.</p><p><bold>Results:</bold> The current meta-analysis had a larger sample size than the previous ones: 99 studies with 43,951 BC and 48,479 controls for <italic>TP53</italic> codon 72 polymorphism, 35 studies with 8,705 BC and 7,516 controls for IVS3 16 bp polymorphism, and 25 studies with 12,222 BC and 12,895 controls for IVS6+62A &gt; G polymorphism. Five gene models were used to explore the association between the three polymorphisms and BC risk, and partial positive results were similar to published meta-analyses results. However, a large number of significant results were considered to be unreliable after correcting with Bayesian false-discovery probability (BFDP), except for the association between <italic>TP53</italic> IVS3 16 bp polymorphism and BC risk in overall analysis (GG vs. CC: BFDP = 0.738), matched studies (GG vs. CC: BFDP = 0.173; GG vs. CC + CG: BFDP = 0.447), and tumor size below 2 cm (GG vs. CC: BFDP = 0.088; GG + CG vs. CC: BFDP = 0.730; GG vs. CC + CG: BFDP = 0.311). These unreliable results were confirmed again without new solid results emerging in further sensitivity analysis (only studies in compliance with the quality assessment standard).</p><p><bold>Conclusion:</bold> After considering the quality of the included studies and the reliability of the results, the present meta-analysis suggested that <italic>TP53</italic> codons 72, IVS3 16 bp, and IVS6+62A &gt; G polymorphisms were not significantly associated with the BC risk. Those results which prove that these three polymorphisms increase BC risk are more likely to be false-positive results due to various confounding factors.</p>