Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas

Galic, Vijaya; Willner, Julia B.; Wollan, Melissa; Garg, Ruchi; Garcia, Rochelle L.; Goff, Barbara A.; Gray, Heidi J.; Swisher, Elizabeth M.

doi:10.1002/gcc.20407

Cited by 50 publications

(33 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In accordance with two previous studies of ovarian cancer (22,23), the G-allele was not associated with younger age at diagnosis in the examined ovarian cancer cases. Bartel et al reported an 8.5-year earlier diagnosis in G/G and T/G as compared to T/T carriers in patients with FIGO III ovarian carcinomas with high estrogen receptor (ER) expression (24).…”

Section: Discussionsupporting

confidence: 92%

“…The prevalence of the homozygous SNP309 variant genotype in our cohort is in line with previous studies in Caucasian patients with ovarian cancer that reported frequencies of 7.8-17.2% (22)(23)(24) and does not significantly differ from the 12% prevalence observed in healthy Caucasians (2). Also, the MDM2 SNP309 has not been linked with ovarian cancer susceptibility of Caucasian women in two case-control studies (22,25).…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

Hofstetter

Berger²,

Bauer³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract.A single nucleotide polymorphism (SNP309) of MDM2 causes elevated MDM2 levels and an attenuation of p53 function. The aim of the present study was to examine the clinical relevance of the MDM2 SNP309 in ovarian cancer. MDM2 SNP309 genotype was analyzed in 198 patients with primary ovarian cancer. MDM2 expression was investigated using immunohistochemistry. A functional yeast-based assay and subsequent sequencing were performed to determine p53 mutational status. Of the patients, 44.4% (88 of 198) exhibited the common variant (T/T), 40.9%

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

Hofstetter

Berger²,

Bauer³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…The presence of this genetic polymorphism brings to the loss of one of the five PXXP repeats (P represents Pro and X represents any amino acid) altering the protein structure and decreasing induction of apoptosis (13). Patients with the Pro allele seem to have a poor prognosis and survival in different tumors, such as breast (14,15), ovarian (16), lung (15), head and neck cancer (15), and esophageal squamous cell carcinoma (17). However, these correlations are not unequivocal (7,18).…”

mentioning

confidence: 99%

Effect of TP53 Arg72Pro and MDM2 SNP309 Polymorphisms on the Risk of High-Grade Osteosarcoma Development and Survival

Toffoli

Biason

Russo

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: The germ-line polymorphisms TP53 Arg72Pro and MDM2 SNP309 T>G are risk factors for tumor development and affect response to chemotherapy and survival in several cancers, but their prognostic and predictive value in patients with high-grade osteosarcomas is not yet defined. The purpose of this study was to investigate the effect of the TP53 Arg72Pro and the MDM2 SNP309 on the risk of osteosarcoma development and survival. Experimental Design: The relative risk to develop osteosarcomas and the overall survival associated to TP53 Arg72Pro and MDM2 SNP309 polymorphisms were investigated in 201 patients. Correlations with event-free survival (EFS) were analyzed in a homogeneous subgroup of 130 patients with high-grade osteosarcomas of the limbs, nonmetastatic at diagnosis, which underwent neoadjuvant chemotherapy. Results: Multivariate analysis showed that the MDM2 polymorphism T309G was associated with an increased risk of developing osteosarcomas [GG versus TT; odds ratio, 2.09; 95% confidence interval (95% CI), 1.15-3.78]. A case/control gender approach evidenced a significant increased risk only for female osteosarcoma patients (GG versus TT; odds ratio, 4.26; 95% CI, 1.61-11.25). Subjects carrying the TP53 Arg72Pro polymorphism were found to have a significantly increased death risk (Pro/Pro versus Arg/Arg; hazard ratio, 2.90; 95% CI, 1.28-6.66). In the subgroup of 130 high-grade osteosarcomas, the TP53 Arg72Pro was an independent marker of EFS (Pro/Pro versus Arg/ Arg; hazard ratio, 2.67; 95% CI, 1.17-6.11). Conclusion:The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53 Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.

show abstract

“…On the other hand, the association of p53 codon 72 genotype with survival has also been investigated in several types of cancer, [24][25][26][27] but few studies have determined the codon 72 genotype and p53 mutations in clinical samples. 8,28,29 Sullivan et al found that patients with a wild-type 72 R tumor are more likely to respond to chemotherapy and display a longer survival than those with a wild-type 72P tumor in 70 advanced head and neck tumors, 8 implying that the association between the codon 72 genotype and survival is modified by p53 gene status.…”

Section: Discussionmentioning

confidence: 99%

Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status

Yao

Zhao

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

In vitro studies suggest that p53 codon 72 genotype alters the apoptotic capacity of p53 protein, with the 72 arginine (R) form of wild-type p53 harboring a greater apoptosis-inducing potential than the 72 proline (P) variant. The aim of this study was to investigate whether the association between the p53 codon 72 genotype and breast cancer survival was modified by p53 gene status. In our study, we examined the p53 codon 72 genotype and p53 mutations (through exons 4-9) in paraffin-embedded specimens from 414 breast cancer patients with a median follow-up of 8.2 years. We report that the p53 codon 72 genotype was significantly associated with disease-free survival (DFS, p 5 0.02) but not with disease-specific survival (DSS, p 5 0.24) in the entire study population (n 5 414). In contrast, the codon 72 genotype was strongly associated with both DFS (p 5 0.001) and DSS (p 5 0.04) among patients with a wild-type p53 tumor (n 5 346), patients with the P/P variant had worse DFS and DSS than did those with the P/R or R/R variant in this subgroup of patients. More importantly, as compared with the P/R or R/R variant, the P/P variant remained an independent prognostic factor of DFS among patients with a wild-type p53 tumor (HR 5 2.5; 95%CI 5 1.4-4.4; p 5 0.003). We conclude that the effect of p53 codon 72 genotype on breast cancer survival is dependent on p53 gene status, the P/P variant is strongly associated with poor prognosis among patients with a wild-type p53 tumor. ' 2008 Wiley-Liss, Inc.Key words: breast cancer; p53 codon 72; p53 mutation; survival p53 tumor suppressor gene plays a central role in the induction of cell cycle arrest, senescence and apoptosis.1 Mutations of the p53 gene are associated with poor clinical outcome in many types of cancer, including breast cancer.2-6 A common polymorphism at codon 72 of p53 gene results in an arginine (R) to a proline (P) change. This polymorphism is located in the proline-rich domain, which is important in the apoptosis function of p53. Studies suggest that the two variants have different biochemical and apoptotic capacity, with the 72 R form of wild-type p53 harboring a greater apoptosis-inducing potential than the 72 P variant of wild-type p53.7-9 These functional differences between the 2 variants may alter the tumor response to systemic chemotherapy and affect the patient's clinical outcome. Our previous study suggested that breast cancer patients with the P/P variant are less likely to respond to primary anthracyclin-based chemotherapy. 10The prognostic role of p53 codon 72 genotype in cancer patient's outcome has not been fully established. A recent study showed that the codon 72 P/P variant is associated with poor clinical outcome in breast cancer, and the association is independent of p53 protein expression.11 This study examined the p53 status by using immunohistochemistry rather than DNA sequencing assay 11 ; however, numerous studies indicate that at least 30% of p53 mutations cannot be detected by immunohistochemistry. 6,12,13 Since in vitro studies stre...

show abstract

Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and clinical outcomes in women with ovarian and peritoneal carcinomas

Cited by 50 publications

References 43 publications

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

MDM2 SNP309 modifies the prognostic significance of the p53 mutational status in patients with ovarian cancer

Effect of TP53 Arg72Pro and MDM2 SNP309 Polymorphisms on the Risk of High-Grade Osteosarcoma Development and Survival

Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status

Contact Info

Product

Resources

About