The Pro Allele of the p53 Codon 72 Polymorphism Is Associated with Decreased Intratumoral Expression of BAX and p21, and Increased Breast Cancer Risk

Proestling, Katharina; Hebar, Alexandra; Pruckner, Nina; Márton, Erika; Vinatzer, Ursula; Schreiber, Martin

doi:10.1371/journal.pone.0047325

Cited by 42 publications

(55 citation statements)

References 49 publications

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“…These results are in agreement with several previous studies, which have reported an increased BC risk in association with Pro/Pro homozygous genotype [21][22][23][24][25][26][27][28]. 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.…”

Section: Discussionsupporting

confidence: 94%

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

et al. 2018

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Background: The purpose of our case control study is to explore the potential association of tumor protein 53 (TP53) c.215G>C, p. (Arg72Pro) polymorphism (rs1042522) with the risk of breast cancer (BC) development in the Moroccan population. Methods and Results: The study population consisted of 125 female patients with confirmed BC and 126 healthy controls. DNA samples were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism assay method using BstUI restriction enzyme. We showed that the homozygous genotype of TP53 72Pro variant was significantly associated with increased BC risk (OR 2.2, 95% CI 1.07–4.54, p = 0.03). The dominant and additive models of TP53 Pro allele were also correlated to the risk of BC (OR 2.13, 95% CI 1.07–4.23, p = 0.02 and OR 1.49, 95% CI 1.03–2.16, p = 0.03, respectively). Furthermore, the TP53 Arg72 variant was associated with protection against BC, either in the homozygous genotype, the dominant or the additive models (OR 0.45, 95% CI 0.22–0.93, p = 0.03; OR 0.46, 95% CI 0.23–0.92, p = 0.029 and OR 0.67, 95% CI 0.46–0.97, p = 0.03, respectively). Conclusion: Our results suggest that TP53 c.215G>C, p. (Arg72Pro) polymorphism may be considered as a genetic marker for predisposition to BC in Moroccan population.

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Section: Discussionsupporting

confidence: 94%

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

et al. 2018

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“…Consequently, we investigated this single nucleotide polymorphism (SNP) in mammary carcinoma. Proestling et al (2012) showed that the p53 protein produced by the Arg-encoding allele appears to be a more potent transcription factor and tumor suppressor in vivo in human BC than the protein produced by the Pro-encoding allele. It has been suggested that the mechanism by which the codon 72 polymorphism increases apoptosis is the enhanced mitochondrial localization of p53 protein in cells with the Arg/Arg genotype; in contrast, the homozygous Pro (Pro/Pro) genotype induces higher levels of G1 arrest compared with the Arg/Arg genotype (Bišof et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer

Almeida¹,

Kleine²,

Camargo-Kosugi³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The association between TP53 gene polymorphisms and breast cancer (BC) in Brazilian women is a controversial topic. In this cross-sectional study, we evaluated the association between clinical pathological variables and three polymorphisms (TP53*11, TP53*72, and TP53*248) in BC patients and controls. Genomic DNA was extracted from the blood cells of 393 participants; the cancer-free control subjects were 26-72 years old (41 ± 11.03) and the BC patients were 28-80 years old (51 ± 10.70). We used standard polymerase chain reaction-restriction fragment length polymorphism and confirmed the results by genetic sequencing. In TP53*11, there was 100% homozygous Glu distribution in both groups. TP53*72 showed genotypic distribution: in the control group, there was 16.10% homozygous Pro, and 42.44% heterozygous and 41.46% homozygous Arg; in the BC group, there was 15.43% homozygous Pro, and 42.55% heterozygous and 42.02% homozygous Arg. The relative frequency of each allele was 0.37% for Pro and 0.63% for Arg in the control group, and 0.37% for Pro and 0.63% for Arg in the BC group. The nuclear grade (P = 0.0084) and adapted histological grade (P = 0.0265) were associated with TP53*72. The distribution of the codon 72 genotypes did not deviate from Hardy-Weinberg equilibrium in either group. In TP53*248, there was 100% homozygous Arg distribution in both groups. In codon 72, the Arg allele is the most prevalent in Brazilian women. TP53*72 may be associated with susceptibility to BC, although more studies are required to evaluate the profile of Brazilian women with BC.

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“…When TP53 is mutated, this effect may be lost, resulting in uncontrolled cell proliferation that may result in tumorigenesis (16). It has been proposed that genetic polymorphisms in TP53 may affect a number of its functions (41).…”

Section: Patient Characteristicsmentioning

confidence: 99%

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

et al. 2017

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Abstract. Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of TP53 and MDM2 polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The IntroductionProstate cancer (PCa) is the most prevalent form of cancer among males in the United States (1). In Iran, the incidence of PCa is ~9.6 cases per 100,000 individuals, with a range of 3.2-16.0 per 100,000 in various geographical settings (2,3). This is comparable with the Asia-Pacific region (9.9 per 100,000), but significantly lower than in the rest of the world (32.8 per 100,000) (4). The median age at diagnosis is ~66 years and the 5-year survival rate of patients with PCa has been estimated to be 98.9% (5).The molecular mechanisms underlying the progression and carcinogenesis of PCa have not yet been clarified. Additional molecular markers that may be employed to detect PCa and to individualize patient therapy and prognosis are of great clinical importance. A number of large cohort and case-control studies with various populations suggest that family history is a primary risk factor for PCa (6-10).In humans, the tumor protein 53 (TP53) gene is located on the short arm of chromosome 17 (17p13.1) (11). TP53, an important tumor suppressor gene, is a crucial regulator of apoptosis and the cell cycle (12-15). When it is mutated, this regulation may be lost, leading to uncontrolled cell proliferation and potentially tumorigenesis (16).The human MDM2 gene is mapped on chromosome 12q14. 3-15 (17). MDM2 functions as a key negative regulator of TP53 (18)

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The Pro Allele of the p53 Codon 72 Polymorphism Is Associated with Decreased Intratumoral Expression of BAX and p21, and Increased Breast Cancer Risk

Cited by 42 publications

References 49 publications

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

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

Analysis of polymorphisms in codons 11, 72 and 248 of TP53 in Brazilian women with breast cancer

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

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