Dataset Information

Association between MDM2 SNP309, p53 Arg72Pro, and hepatocellular carcinoma risk: A MOOSE-compliant meta-analysis.

ABSTRACT: Epidemiological studies have determined the associations between polymorphisms on the promoter of MDM2 (SNP309) and the codon 72 on exon 4 of p53 (p53 Arg72Pro) and the risk of hepatocellular carcinoma (HCC); however, the results were not always consistent. The aim of the present meta-analysis was to evaluate the overall associations between these 2 variants and HCC risk.The MEDLINE, Web of science, EMBASE, Cochrane Library, and CNKI databases were searched for eligibility studies and the data were synthesized under the fixed- or random-effects model. Heterogeneity among the studies was evaluated with the Cochrane test Q and I statistic.For MDM2 SNP309, the pooled odds ratio (OR) from 15 independent studies with a total of 4038 cases and 5491 controls suggested a significant association for the variant with HCC risk [allele model, G vs T: pooled OR?=?1.48, 95% confidence interval (95% CI)?=?1.26-1.73; pooled OR?=?1.53, 95% CI?=?1.26-1.81, for G/T vs T/T; pooled OR?=?2.04, 95% CI?=?1.54-2.71 for G/G vs T/T]. For p53 Arg72Pro, a total of 21 studies with 7285 cases and 9710 controls suggested that the variant was also associated with HCC risk under common genetic model (allele Pro vs Arg, pooled OR?=?1.13, 95% CI?=?1.02-1.25; Pro/Pro vs Arg/Arg, pooled OR?=?1.32, 95% CI =1.06-1.64). No publication bias was found for all the meta-analysis as suggested by the Begg funnel plot and Egger tests.These results suggested that variants MDM2 SNP309 and p53 Arg72Pro are susceptibility factors for HCC; however, more studies are warranted to validate the results.

SUBMITTER: Duan X

PROVIDER: S-EPMC6392589 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Association between MDM2 SNP309, p53 Arg72Pro, and hepatocellular carcinoma risk: A MOOSE-compliant meta-analysis.

Duan Xiaohua X Li Jingquan J

Medicine 20170901 36

Epidemiological studies have determined the associations between polymorphisms on the promoter of MDM2 (SNP309) and the codon 72 on exon 4 of p53 (p53 Arg72Pro) and the risk of hepatocellular carcinoma (HCC); however, the results were not always consistent. The aim of the present meta-analysis was to evaluate the overall associations between these 2 variants and HCC risk.The MEDLINE, Web of science, EMBASE, Cochrane Library, and CNKI databases were searched for eligibility studies and the data w ...[more]

PMID: 28885338

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Project description:BACKGROUND:Murine double minute 2 homolog (MDM2) plays an important role in the downregulation of P53 tumor suppressor gene. MDM2 inhibits P53 transcriptional activity and thereby results in accelerated tumor formation. Overexpression of MDM2 has been found in several cancer types including endometrial cancer. SNP309 is located in the promoter region of MDM2 and contributes to the overexpression of MDM2. The association between MDM2 SNP309 polymorphism and endometrial cancer risk has been investigated in several studies; however, the conclusion remains controversial. OBJECTIVES:We performed the present meta-analysis to give a comprehensive conclusion of the association between MDM2 SNP309 polymorphism and endometrial cancer susceptibility. METHODS:We conducted a literature research on PubMed, Embase, Cochrane Library, OVID, Web of Science, Wan Fang, CNKI, and CQVIP databases up to July 31, 2018. Newcastle-Ottawa scale was used to assess the quality of studies. We evaluated the strength of association by combining odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models under a fixed-effect model or random-effect model. We further conducted subgroup analysis by ethnicity, source of control, histological type, clinical type, grade, and stage of tumor. Sensitivity analysis and publication bias were also performed. RESULTS:Nine eligible studies were finally included in our meta-analysis. We found MDM2 SNP309 polymorphism increased the risk of endometrial cancer under allele model (OR: 1.23, 95% CI: 1.06-1.41, P?=?.005), homozygote model (OR: 1.43, 95% CI: 1.13-1.81, P?=?.003) and recessive model (OR: 1.55, 95% CI: 1.17-2.04, P?=?.002). Subgroup analysis suggested a similar elevated risk in both Asians and Caucasians. We identified a strong association of enhanced susceptibility to endometrial cancer in endometrioid group (OR: 2.13, 95% CI: 1.28-3.54, P?=?.004) and Type I group (OR: 1.89, 95% CI: 1.25-2.86, P?=?.002) under dominant model. We identified no significant publication bias according to Egger's test. CONCLUSIONS:Our meta-analysis suggested that MDM2 SNP309 polymorphism increased the risk of endometrial cancer significantly, especially in endometrioid and Type I endometrial cancer, indicating MDM2 could serve as a potential diagnostic factor marker for endometrial cancer.

Project description:BackgroundUrinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.MethodsAfter re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.ResultsOf the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).ConclusionsMDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.

Dataset Information

Association between MDM2 SNP309, p53 Arg72Pro, and hepatocellular carcinoma risk: A MOOSE-compliant meta-analysis.

Publications

Association between MDM2 SNP309, p53 Arg72Pro, and hepatocellular carcinoma risk: A MOOSE-compliant meta-analysis.

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