Impact of MDM2 polymorphism

Chaar, Ines; Arfaoui, Toumi Amira; Amine, El Hadj Olfa El; Mahmoud, L Ben; Khiari, M.; Sammoud, Soraya; Lounis, Mohamed Amine; Amara, Semeh; Gharbi, Lassad; Hmida, Abdelmajid Ben; Mzabi, Sabeh; Bouraoui, Saâdia

doi:10.1097/meg.0b013e32834bdf84

Cited by 13 publications

(17 citation statements)

References 43 publications

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“…In the total population, no statistical association between the MDM2 SNP309 polymorphism and CRC risk were found in all genetic models under random-effects model ( P value for heterogeneity < 0.1). Thus we used a Galbraith plot to investigate the source of heterogeneity and found one article with an European population21, which could potentially be the cause of high heterogeneity (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…Some studies show that the TG genotype is associated with higher CRC risk than the TT genotype192021, whereas, others show no association2223. Recently, Zhang et al .…”

Section: Discussionmentioning

confidence: 99%

“…The databases of PubMed, Embase and Web of Science updated on April 1, 2013, were searched for articles based on the human associated case-control studies in English, using the terms: “MDM2”, “polymorphism(s) or genetic variation(s)”, “colorectal” and “cancer or carcinoma or tumor” as well as their combinations. Finally, we collected 11 studies consisting of a total of 3171 cases and 2597 controls19202122232426272829. Because the studie published by Chaar21 was found to be the potential cause of high heterogeneity, we excluded this study and analyzed the rest again.…”

Section: Methodsmentioning

confidence: 99%

“…Finally, we collected 11 studies consisting of a total of 3171 cases and 2597 controls19202122232426272829. Because the studie published by Chaar21 was found to be the potential cause of high heterogeneity, we excluded this study and analyzed the rest again. ORs and 95% CIs were used to determine the strength of association between MDM2 SNP309 and CRC risk, and we used Z -tests to estimate the statistical significance of the pooled OR.…”

Section: Methodsmentioning

confidence: 99%

“…Many studies have evaluated this association in different tumors, but their results are conflicting161718. Some studies have reported a direct connection between MDM2 SNP309 and CRC risk192021; however others have shown the opposite2223.…”

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confidence: 99%

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MDM2 SNP309 polymorphism is associated with colorectal cancer risk

Wang

et al. 2014

Sci Rep

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The human murine double minute 2 (MDM2) is known as an oncoprotein through inhibiting P53 transcriptional activity and mediating P53 ubiquitination. Therefore, the amplification of MDM2 may attenuate the P53 pathway and promote tumorigenesis. The SNP309 T>G polymorphism (rs2279744), which is located in the intronic promoter of MDM2 gene, was reported to contribute to the increased level of MDM2 protein. In this hospital-based case-control study, which consisted of 573 cases and 588 controls, we evaluated the association between MDM2 SNP309 and the risk of colorectal cancer (CRC) in a Chinese population by using the TaqMan method to genotype the polymorphism. We found that the MDM2 SNP309 polymorphism was significantly associated with CRC risk. In addition, in our meta-analysis, we found a significant association between MDM2 SNP309 and CRC risk among Asians, which was consistent with our results. In conclusion, we demonstrated that the MDM2 SNP309 polymorphism increased the susceptibility of CRC in Asian populations.

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Section: Resultsmentioning

confidence: 99%

“…Some studies show that the TG genotype is associated with higher CRC risk than the TT genotype192021, whereas, others show no association2223. Recently, Zhang et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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MDM2 SNP309 polymorphism is associated with colorectal cancer risk

Wang

et al. 2014

Sci Rep

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Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

et al. 2019

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Background The murine double minute‐2 gene ( MDM2 ) was originally identified as predicting chemotherapy efficacy. However, little is known regarding the association between single nucleotide polymorphisms (SNPs) in the p53 signaling pathway and prognosis/chemotherapy sensitivity in colorectal cancer. Methods We analyzed the association between 111 SNPs in 22 p53 signaling pathway genes and both progression‐free survival (PFS) and disease control rate (DCR) using Cox regression and logistics regression analysis. The false discovery rate method was used for correction of multiple testing. Secondary structure was predicted by RNAfold. Expression qualitative trait locus analysis and mRNA expression differences were assessed using the GTEx and TCGA databases. Results We found that the rs747828 C allele of TP73 was significantly associated with reduced PFS (HR = 1.64, 95% CI = 1.27‐2.12, P = 2.00 × 10 −4 ) in the additive model. In the stratified analysis, the rs747828 C allele was significantly associated with both reduced PFS ( P = 1.40 × 10 −3 ) and DCR ( P = 1.82 × 10 −2 ) in oxaliplatin‐based chemotherapy. The secondary structure of TP73 was altered in response to different rs747828 genotypes. Although the rs747828 C allele was not associated with messenger RNA (mRNA) TP73 expression, it was significantly associated with increased mRNA TP73‐AS1 expression levels in sigmoid tissues. TP73 mRNA was significantly overexpressed in tumor tissues compared to adjacent normal tissues ( P = 2.36 × 10 −19 ). Conclusion Our findings indicate that functional genetic variants of TP73 mediate the response to chemotherapy in colorectal cancer.

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TP53 Arg 72Pro and MDM2 SNP309 Polymorphisms and Colorectal Cancer Risk: A West Algerian Population Study

Abderrahmane

Louhibi

Moghtit

et al. 2014

Pathol. Oncol. Res.

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The tumor suppressor gene TP53 and its regulator MDM2 are both key players involved in multiple pathways including apoptosis, cellular transcriptional control and cell cycle regulation. Common germline polymorphisms in these genes may affect colorectal cancer (CRC) susceptibility. An arginine-to-proline substitution at codon 72 in the TP53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309 (named SNP309) of murine double minute 2 MDM2 gene increases its transcription. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer in the Algerian population was addressed in this study. DNA samples from 121 controls and 116 cases were genotyped for these two polymorphisms by PCR/RFLP then confirmed by sequencing. Unexpectedly no significant association was found between this potential marker TP53 Arg72Pro and CRC (p > 0.05). However, our findings reveal that individuals with the MDM2 SNP309 GG genotype have a low risk of CRC as compared to the TT genotype (OR = 0.49; 95 % CI: 0.24-0.98, p = 0.04), with more significance for females (OR = 0.16; 95 % CI: 0.06-0.41, p < 0.05). Moreover, no significant association was observed between the combined TP53 and MDM2 genotypes and CRC. Contrary to initial expectations that the GG genotype with high MDM2 levels would increase cancer risk, our results demonstrate that the MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer. This is suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.

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Impact of MDM2 polymorphism

Abstract: Our results suggest that the MDM2 polymorphism is significantly associated with colorectal cancer risk and may provide useful prognostic information for Tunisian patients with colorectal cancer.

Cited by 13 publications

References 43 publications

MDM2 SNP309 polymorphism is associated with colorectal cancer risk

MDM2 SNP309 polymorphism is associated with colorectal cancer risk

Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer

TP53 Arg 72Pro and MDM2 SNP309 Polymorphisms and Colorectal Cancer Risk: A West Algerian Population Study

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