The role of a single nucleotide polymorphism of MDM2 in glioblastoma multiforme

Khatri, Rina; Navaratne, Kapila; Weil, Robert J.

doi:10.3171/jns/2008/109/11/0842

Cited by 18 publications

(20 citation statements)

References 32 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Support for the model has come from the association of MDM2 SNP309 with differences in the onset of, or the risk for, cancer, as well as survival (2,3,18). For example, earlier ages of onset associated with individuals possessing the G-allele have been demonstrated in softtissue sarcomas (1,19,20), lymphoma (21), leukemia (22), melanoma (23), head, neck, and oral squamous cell carcinomas (24,25), and cancers of the colon (26), breast (21,27,28), bladder (29), ovary (30), brain (31), and liver (32).…”

mentioning

confidence: 99%

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

Atwal

Kirchhoff

Bond

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A large body of evidence strongly suggests that the p53 tumor suppressor pathway is central in reducing cancer frequency in vertebrates. The protein product of the haploinsufficient mouse double minute 2 (MDM2) oncogene binds to and inhibits the p53 protein. Recent studies of human genetic variants in p53 and MDM2 have shown that single nucleotide polymorphisms (SNPs) can affect p53 signaling, confer cancer risk, and suggest that the pathway is under evolutionary selective pressure ( 1 – 4 ). In this report, we analyze the haplotype structure of MDM4, a structural homolog of MDM2, in several different human populations. Unusual patterns of linkage disequilibrium (LD) in the haplotype distribution of MDM4 indicate the presence of candidate SNPs that may also modify the efficacy of the p53 pathway. Association studies in 5 different patient populations reveal that these SNPs in MDM4 confer an increased risk for, or early onset of, human breast and ovarian cancers in Ashkenazi Jewish and European cohorts, respectively. This report not only implicates MDM4 as a key regulator of tumorigenesis in the human breast and ovary, but also exploits for the first time evolutionary driven linkage disequilibrium as a means to select SNPs of p53 pathway genes that might be clinically relevant.

show abstract

mentioning

confidence: 99%

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

Atwal

Kirchhoff

Bond

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…However, other studies have reported no association between the variant and glioma risk (Wang et al, 2004;Malmer et al, 2005). With respect to MDM2 SNP309, 2 reports have found no correlation with glioma risk (El Hallani et al, 2007;Tsuiki et al, 2007), whereas a study conducted by Khatri et al (2008) has found that allele G may be a low-penetrance susceptibility allele for glioblastoma multiforme.…”

Section: Introductionmentioning

confidence: 78%

“…Among them, studies reported by El Hallani et al (2007) and Tsuiki et al (2007) found no significant association between the MDM2 SNP309 variant and glioma risk. The study conducted by Khatri et al (2008) with 98 glioblastoma multiforme patients and 102 cancer-free controls showed that allele G confers an increased risk of glioma; however, the study showed significant deviation from HWE for the allele distribution in the control group (P < 0.001).…”

Section: Association Between Mdm2 Snp309 and Glioma Riskmentioning

confidence: 99%

“…No significant publication bias was found in the meta-analysis. The study conducted by Khatri et al (2008) showed a departure from HWE, and we excluded this study from further analysis. However, no significant change in the results was found after the exclusion.…”

Section: Association Between Mdm2 Snp309 and Glioma Riskmentioning

confidence: 99%

“…Three studies evaluating the association of MDM2 SNP309 and glioma risk were identified in our literature search (El Hallani et al, 2007;Tsuiki et al, 2007;and Khatri et al, 2008;see Table 2). The 3 reports had recruited 606 cases and 390 controls.…”

Section: Association Between Mdm2 Snp309 and Glioma Riskmentioning

confidence: 99%

See 2 more Smart Citations

Association of p53 Arg72Pro and MDM2 SNP309 polymorphisms with glioma

Sh²,

Xh³

et al. 2012

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Epidemiological studies of the association of variants p53 Arg72Pro and MDM2 single-nucleotide polymorphism 309 (SNP309) with glioma risk have produced inconsistent results. The aim of the current study was to evaluate the association of these 2 variants with glioma susceptibility using a meta-analysis approach. For p53 Arg72Pro, 10 case-control studies including 2587 glioma patients and 4061 unrelated controls were identified. The pooled odds ratios (ORs) for Arg/Pro heterozygotes and Pro/Pro homozygotes were 1.08 [95% confidence interval (95%CI) = 0.85-1.37] and 1.08 (95%CI = 0.85-1.36), respectively, when compared to Arg/Arg carriers. Under the dominant effect model, Pro allele carriers also showed no significantly elevated glioma risk (pooled OR = 1.11, 95%CI = 3619 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 3618-3628 (2012) p53 and MDM2 polymorphisms and glioma susceptibility 0.90-1.38), and similar results were found under the recessive-effect model (pooled OR = 1.17, 95%CI = 0.85-1.61). For variant MDM2 SNP309, 3 case-control studies including 606 cases and 309 controls were identified. A marginal association with glioma risk was found for heterozygous G/T carriers (pooled OR = 1.95, 95%CI = 1.00-3.81), whereas homozygous G/G carriers showed an increased but not significantly elevated risk of glioma (pooled OR = 2.14, 95%CI = 0.71-6.45) compared with that of T/T homozygotes. We also found no significant association between the MDM2 SNP309 polymorphism and glioma risk (pooled OR = 1.86, 95%CI = 0.94-3.67 and pooled OR = 1.25, 95%CI = 0.62-2.56, respectively) under the dominant and recessive models. Taken together, the current data suggested that the 2 polymorphisms may not contribute to glioma susceptibility.

show abstract

CNSCancers

Graeme

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

CNS tumors represent a diverse collection of tumor types driven by a range of signaling inputs that often generate highly aggressive and at the same time heterogeneous tumor types. The effect of these tumors is particularly dramatic and impacts on children as well as adults. Malignant CNS tumors are characterized by being highly heterogeneous, aggressive, and frequently invasive, leading to poor overall patient survival times. As CNS tumors present within the nervous system, there are particular challenges in the development of effective molecular‐targeted therapies in dealing not only with the aggressive nature of these tumors and their ability to evade treatment but also, particularly, with maintaining normal neuronal and brain functions. Compounding this is the need to deliver systemically small molecules or other agents such as vaccines and for immunotherapy approaches to confront the complexity of the relationship between the nervous system and the immune system. Research to find effective treatments for CNS tumors is being facilitated by two key inputs both of which are reviewed in this chapter; first, a much greater understanding of tumor pathobiology and the potential role of developmental signaling pathways and tumor stem‐like cells, and by the development of animal models that more adequately represent endpoints measurable in the clinic. Together, these advances should assist in the selection of better targets and the optimization of better compounds to progress into clinical trials.

show abstract

The role of a single nucleotide polymorphism of MDM2 in glioblastoma multiforme

Abstract: Although the MDM2 SNP309 does not portend decreased survival, the increased incidence of the mutant G allele in patients with GBM and its influence on age of onset suggest a potential role in the molecular pathogenesis of GBM, and may be a therapeutic target.

Cited by 18 publications

References 32 publications

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

Association of p53 Arg72Pro and MDM2 SNP309 polymorphisms with glioma

CNSCancers

Contact Info

Product

Resources

About