Association of the TP53 codon 72 polymorphism and breast cancer risk: a meta-analysis

Abstract

This study was conducted in order to investigate the implications of the R72P polymorphism in the TP53 gene in breast cancer risk. The enlightenment of this matter might provide a piece of information about the potential implications of this polymorphism in patient risk. A meta-analysis was conducted considering a large sample size from studies with conflicting results on the R72P polymorphism in breast cancer patients. Relevant studies were selected from PubMed and SciELO databases for data extraction and statistical analysis. Database was built according to the continent and considering the genotype frequencies, sample size and genotyping methodology. The dominant models (RR vs RP + PP and RR + RP vs. PP), homozygous (RR vs. PP), heterozygous (RR vs. RP and RP vs. PP) and the allele (R vs. P) were used. Genotype frequencies were summarized and evaluated by χ2 test of heterogeneity in 2×2 contingency tables with 95% CIs. Odds Ratios (OR) were calculated with a fixed-effect model (Mantel-Haenszel) or a random-effect model (DerSimonian-Laird) if the studies were considered homogeneous (P > 0.05) or heterogeneous (P < 0.05), respectively, using BioEstat® 5.0 software. Supported by a large sample size composed by 25,629 cases and 26,633 controls from 41 studies, we found significant association between the R72P polymorphism in the TP53 gene and the breast cancer risk. The overall data shows an increased risk due to the P allele dominant model, but not in Asia where the risk was associated with the R allele and R dominant model.

Association of p53 Codon 72 Polymorphism with Breast Cancer in a Rwandese Population

“…Our results are in agreement with previously reported data in different populations [25-29]. The meta-analysis conducted by Gonçalves et al [30] showed that breast cancer patients and control subjects were mainly heterozygous in the Asian population (50.1 and 48.0%, respectively) and the African population (43.9 and 49.7%, respectively), whereas the homozygote Arg/Arg was predominant in America (53.6 and 54.5%, respectively) and Europe (54.1 and 53.4%, respectively). However, the Pro/Arg heterozygous genotype was found to be higher in a Saudi population among healthy women (60.19%) than in women with breast cancer (25%) [31], while the Pro/Arg genotype has been reported to be associated with breast cancer risk in an Iranian population, with 75.55% in breast cancer cases versus 62% in controls [32].…”

The 72Pro Variant of the Tumor Protein 53 Is Associated with an Increased Breast Cancer Risk in the Moroccan Population

“…Similarly, Tp53 Pro allele has been found to be associated with BC risk in North Indian [23], Austrian [22], Bangladeshi [28], Iranian [21], Turkish [30], Spanish [32], Swedish [26], American [34], German [33], Russian [36], Japanese [25], and Slovakian [35] populations. In addition, a meta-analysis performed by Gonçalves et al [31], involving 25629 BC cases and 26.633 controls from 41 studies, reported an increased BC risk due to TP53 Pro allele dominant model, but not among Asian subgroup where the risk was associated with TP53 Arg allele and the Arg dominant model.…”

TP53 Codon 72 Genetic Polymorphism, rs1042522, Modifies the Association Between Tobacco Smoking and Breast Cancer Risk

“…In contrast, the proline variant has been found to have a higher ability to induce DNA-repair and cell cycle arrest (7,8); nevertheless, it has been observed that in the context of p53 mutations, cells that express mtp53-codon72-Pro have greater apoptotic potential (9,10). Concerning the association between TP53 codon72 polymorphism and the risk of breast cancer, studies have revealed conflicting results (11)(12)(13).…”

“…Consistent with these studies, our statistical evidence revealed that none of the codon72 genotypes is associated with breast cancer in southern Iranian women, suggesting that probably this polymorphism does not impress the risk of breast cancer directly. Nevertheless, Goncalves et al in a metaanalysis of forty-one case-control studies suggested an increased risk of breast cancer due to PP genotype (R vs. P; OR = 1.02; 95% CI 1.00 -1.05), although in Asians they demonstrated that the risk was associated with the R allele (R vs. P; OR = 1.09; 95% CI 1.01 -1.17) (11).…”