Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients

Yadav, Prasant; Masroor, Muhammad; Tanwer, K.; Mir, Rashid; Javid, Jamsheed; Ahmad, Istaq; Zuberi, Mariyam; Kaza, R. C. M.; Jain, Shyama; Khurana, Nita; Ray, P. C.; Saxena, Alpana

doi:10.1007/s12094-015-1425-5

Cited by 14 publications

(22 citation statements)

References 32 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Indeed, rs1800372 is associated with poor outcome in primary breast cancer (47), and synonymous variants in the mouse Trp53 gene have been shown to influence binding of the Trp53 transcript to MDM2 and subsequent p53 function (48). Similarly, the R72P p53 variant (rs1042522), which is not classified as a deleterious mutation, has also been implicated in cancer susceptibility in humans (49). To our knowledge, this analysis is the first multi-omics analysis of SMNs and determination of germline TP53 variants in survivors of pediatric malignancies.…”

Section: Discussionmentioning

confidence: 99%

Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors

Sherborne

Lavergne

et al. 2017

Clinical Cancer Research

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Purpose Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design We performed whole exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in thirty-seven pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without history of a familial cancer predisposition syndrome but known to have developed SMNs. Results WES revealed TP53 mutations involving p53’s DNA binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53 mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53 coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in six patients and a synonymous single nucleotide polymorphism A639G in four others, resulting in ten out of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions Currently, germline TP53 is not routinely assessed in pediatric cancer patients. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive post-treatment monitoring.

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“…To maintain the stability of the meta-analysis after the non-inclusion of deviant studies of HWE and sensitivity analysis, we evaluated the influence of each study on pooled OR. After the exclusion of studies [39][40][41][42], no study has shown a significant influence of the pooled OR effect in each of the different genetic models ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…This bias existed in mostly studies whose distribution of Arg/Arg, Arg/Pro and Pro/Pro genotypes in controls was not in HWE [59][60][61][62][63][64][65][66][67][68][69][70][71][72].We also performed an in-depth sensitivity analysis by removing each single study from the pooled data and the results showed that there was no influence of the individual data on the overall results. In addition, we also calculated the overall combined OR on the additive model (Pro vs Arg) with and without the four studies which influenced the values of the Odds ratio [39][40][41][42], and in both cases, we found that the Pro allele was associated with a high risk of developing breast cancer. The major advantage of this meta-analysis was the inclusion of a large number of samples including very selective criteria.…”

Section: Discussionmentioning

confidence: 99%

TP53 p.Arg72Pro polymorphism and Breast Cancer Risk: A meta-analysis of case-control studies

Diakité¹,

Kassogue²,

Dolo³

et al. 2020

Preprint

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Background :The effect of the p.Arg72Pro variant of the P53 gene on the risk of developmentof breast cancer remains variable in populations. However, the use of strategiessuchas pooling age-matched controls with disease cases may provide a solid meta-analysis. Our goal was to perform a meta-analysis in order to assessthe association of p.Arg72Provariant of P53 gene with breast cancer risk. Methods : Databases such as PubMed, Genetics Medical Literature, Harvard University Library, Web of Science and Genesis Library were used to search articles. Age-matched case-control studies on breast cancer that have evaluated the genotype frequencies of the p.Arg72Pro of P53 gene 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 cases age-matched controls including7841disease cases and 8876controls were evaluated in this meta-analysis. Overall, our results suggested that p.Arg72ProP53 was associated with a risk for 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 in the recessive model (OR = 1.07, 95% CI = 0.97-1.16; P= 0.19). According to the ethnic group, allele Pro has been associated with breast cancer risk in Europeans for the dominant and additive models. Conclusions : This meta-analysis found a significant association between p.Arg72Pro in the P53 gene and the risk of breast cancer. Individuals carrying at least one Pro allele of the P53 gene are more likely to have breast cancer with dominant and additive models than individualsharboringthe Arg allele.

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Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients

Cited by 14 publications

References 32 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

Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors

TP53 p.Arg72Pro polymorphism and Breast Cancer Risk: A meta-analysis of case-control studies

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