p.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies

Abstract

Background The effect of the p.Arg72Pro variant of the P53 gene on the risk of development ofbreast cancer remains variable in populations. However, the use ofstrategies such aspoolingage-matched controls with disease may provide a consistent meta-analysis. Our goal was to perform a meta-analysis in order to assess the association of p.Arg72Pro variant of P53 gene with the risk of breast cancer. Methods Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Case-control studies with age-matched on breast cancer havingevaluated the genotype frequencies of the TP53 p.Arg72Pro polymorphism were selected. The fixed and random effects (Mantel-Haenszel) were calculated using pooled odds ratio of 95% CI to determine the risk of disease. Inconsistency was calculated to determine heterogeneity among the studies. The publication bias was estimated using the funnel plot. Results Twenty-one publications with 7841 cases and 8876 controls were evaluated in this meta-analysis. Overall, our results suggested that TP53 p.Arg72Pro was associated with the risk of breast cancer for the dominant model (OR = 1.09, 95% CI = 1.02–1.16, P = 0.01) and the additive model (OR = 1.09, 95% CI = 1.01–1.17, P = 0.03), but not for the recessive model (OR = 1.07, 95% CI = 0.97–1.18, P = 0.19). According to the ethnic group analysis, Pro allele was associated with the risk of breast cancer in Caucasians for the dominant model and additive model (P = 0.02), and Africans for the recessive model and additive model (P = 0.03). Conclusions This meta-analysis found a significant association between TP53 p.Arg72Pro polymorphism and the risk of breast cancer. Individuals carrying at least one Pro allele were more likely to have breast cancer than individuals harboring the Arg allele.

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

“…The results of the published meta-analyses on the association between TP53 codon 72, IVS3 16 bp, and IVS6+62A > G polymorphisms and BC risk in different ethnic groups are shown in Supplementary Table S5 and the cells highlighted with red color indicated significant results. Two studies ( Dunning et al, 1999 ; Diakite et al, 2020b ) showed that the codon 72 polymorphism increased BC risk in overall analysis. In the ethnic subgroup analyses of the association between codon 72 polymorphism and BC risk, one study ( Gonçalves et al, 2014 ) found that the polymorphism significantly increased BC risk in Asians, and another study ( Diakite et al, 2020b ) indicated an obviously increased BC risk in Caucasians.…”

“…Two studies ( Dunning et al, 1999 ; Diakite et al, 2020b ) showed that the codon 72 polymorphism increased BC risk in overall analysis. In the ethnic subgroup analyses of the association between codon 72 polymorphism and BC risk, one study ( Gonçalves et al, 2014 ) found that the polymorphism significantly increased BC risk in Asians, and another study ( Diakite et al, 2020b ) indicated an obviously increased BC risk in Caucasians. With respect to the TP53 IVS3 16 bp polymorphism, 6 studies ( Dunning et al, 1999 ; Hu et al, 2010a ; Hu et al, 2010b ; He et al, 2011 ; Sagne et al, 2013 ; Wu et al, 2013 ; Diakite et al, 2020a ) found an obviously increased BC risk in overall analysis.…”

“…Supplementary Table S5 shows the published meta-analysis results of the association between TP53 codon 72, IVS3 16 bp and IVS6+62A > G polymorphisms and BC risk. Published meta-analyses ( Dunning et al, 1999 ; Gonçalves et al, 2014 ; Diakite et al, 2020b ) indicated that the TP53 codon 72 polymorphism significantly increased BC risk in overall analysis, Asians, Caucasians (cells highlighted with red color in Supplementary Table S5 ). Previous meta-analyses ( Dunning et al, 1999 ; Hu et al, 2010a ; Hu et al, 2010b ; He et al, 2011 ; Sagne et al, 2013 ; Wu et al, 2013 ; Diakite et al, 2020a ) had only reported TP53 IVS3 16 bp polymorphism with an increased BC risk in overall analysis and only one study ( Wu et al, 2013 ) performed the analyses stratified by ethnicity.…”

“…Furthermore, only four previous meta-analyses ( He et al, 2011 ; Cheng et al, 2012 ; Dahabreh et al, 2013 ; Hou et al, 2013 ) checked the duplicate of studies. Third, all previous meta-analyses ( Dunning et al, 1999 ; Suspitsin et al, 2003 ; Zhuo et al, 2009 ; Hu et al, 2010a ; Hu et al, 2010b ; Zhang et al, 2010 ; Francisco et al, 2011 ; He et al, 2011 ; Ma et al, 2011 ; Cheng et al, 2012 ; Dahabreh et al, 2013 ; Hou et al, 2013 ; Sagne et al, 2013 ; Wu et al, 2013 ; Gonçalves et al, 2014 ; Diakite et al, 2020a ; Diakite et al, 2020b ) did not adjust positive results for multiple comparisons and did not conduct subgroup analysis with clinical presentations. Fourth, some published meta-analyses did not perform sensitivity analyses.…”

“…Although these three polymorphisms have been reported by 108 studies, the relationship between the three SNPs and BC risk remains unclear, because of small sample size and contradictory results. Furthermore, seventeen meta-analyses ( Dunning et al, 1999 ; Suspitsin et al, 2003 ; Zhuo et al, 2009 ; Hu et al, 2010a ; Hu et al, 2010b ; Zhang et al, 2010 ; Francisco et al, 2011 ; He et al, 2011 ; Ma et al, 2011 ; Cheng et al, 2012 ; Dahabreh et al, 2013 ; Hou et al, 2013 ; Sagne et al, 2013 ; Wu et al, 2013 ; Gonçalves et al, 2014 ; Diakite et al, 2020a ; Diakite et al, 2020b ) have been published and tried to describe the connection between TP53 codons 72, IVS3 16 bp, and IVS6+62A > G polymorphisms and BC risk, but their results tended to be contradictory and heterogeneous. Moreover, TP53 polymorphisms based on patient clinical characteristics were not considered in all these published meta-analyses.…”