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Have the roles of two functional polymorphisms in breast cancer, R72P in P53 and MDM2-309 in MDM2, become clearer?

ABSTRACT: Genetic differences between individuals have been predicted to account for disparate outcomes in patients diagnosed with cancer. The search for genetic determinants has been ongoing for a considerable amount of time and it is only now that insights have been gained into which polymorphisms are most likely to be important in determining not only disease likelihood but also outcome. The quest to be able to accurately predict patient outcomes in breast cancer may now be a step closer as increased sample size is leading to more robust statistical analysis and a better understanding of molecular mechanisms of disease are forthcoming.

SUBMITTER: Scott RJ

PROVIDER: S-EPMC2880429 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Have the roles of two functional polymorphisms in breast cancer, R72P in P53 and MDM2-309 in MDM2, become clearer?

Scott Rodney J RJ

Breast cancer research : BCR 20100203 1

Genetic differences between individuals have been predicted to account for disparate outcomes in patients diagnosed with cancer. The search for genetic determinants has been ongoing for a considerable amount of time and it is only now that insights have been gained into which polymorphisms are most likely to be important in determining not only disease likelihood but also outcome. The quest to be able to accurately predict patient outcomes in breast cancer may now be a step closer as increased s ...[more]

PMID: 20156327

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Combined effects of MDM2 SNP309 and TP53 R72P polymorphisms, and soy isoflavones on breast cancer risk among Chinese women in Singapore.

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| S-EPMC3404431 | biostudies-literature

Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma.

Project description:Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.

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The R72P P53 mutation is associated with familial breast cancer in Jewish women.

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The frequency of TP53 R72P and MDM2 309T>G polymorphisms in Iranian infertile men with spermatogenetic failure: A case-control study.

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MDM2, MDM2-C, and mutant p53 expression influence breast cancer survival in a multiethnic population.

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P53 mdm2 inhibitors.

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| S-EPMC3719986 | biostudies-literature

The roles and regulation of MDM2 and MDMX: it is not just about p53.

Project description:Most well studied as proteins that restrain the p53 tumor suppressor protein, MDM2 and MDMX have rich lives outside of their relationship to p53. There is much to learn about how these two proteins are regulated and how they can function in cells that lack p53. Regulation of MDM2 and MDMX, which takes place at the level of transcription, post-transcription, and protein modification, can be very intricate and is context-dependent. Equally complex are the myriad roles that these two proteins play in cells that lack wild-type p53; while many of these independent outcomes are consistent with oncogenic transformation, in some settings their functions could also be tumor suppressive. Since numerous small molecules that affect MDM2 and MDMX have been developed for therapeutic outcomes, most if not all designed to prevent their restraint of p53, it will be essential to understand how these diverse molecules might affect the p53-independent activities of MDM2 and MDMX.

| S-EPMC8091979 | biostudies-literature

Ubiquitin receptors play redundant roles in the proteasomal degradation of the p53 repressor MDM2.

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