MDM2 T309G polymorphism and esophageal cancer risk: a meta-analysis.
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ABSTRACT:
SUBMITTER: Lei C
PROVIDER: S-EPMC4612961 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
MDM2 T309G polymorphism and esophageal cancer risk: a meta-analysis.
Lei Caipeng C Zhang Weiguo W Fan Junli J Qiao Bin B Chen Qiang Q Liu Qin Q Zhao Chunling C
International journal of clinical and experimental medicine 20150815 8
Murine double minute 2 (MDM2) has suggested to play an important role in esophageal cancer. The association between MDM2 T309G polymorphism and esophageal cancer risk was inconclusive. To clarify the possible association, we conducted a meta-analysis. We searched in the PubMed, Embase, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. A total of 6 studies with 4909 cases and controls were included based on the search cri ...[more]
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Project description:BackgroundThe aim of this study was to investigate the correlation between MDM2 T309G single nucleotide polymorphism (SNP) and esophageal cancer susceptibility through pooling the open published data.MethodsBy systematic searching the databases of Medline, EMBASE, CBM and CNKI, the case-control or cohort studies related to MDM2 T309G single nucleotide polymorphism and esophageal cancer risk were screened. Genetic phenotype data of T309G single nucleotide was extracted from the original included studies. The correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility was demonstrated by the odds ratio (OR) and its corresponding 95% confidence interval (95% CI). Publication bias was investigated by Egger's line regression test and begg's funnel plot.ResultsAfter systematic searching of the relevant database, nine publications were finally included in the present study. The combined data demonstrated that the subjects with the G genotype had an increased risk of developing esophageal cancer in dominant (OR = 1.13, 95% CI: 1.00-1.27, P = 0.043), recessive (OR = 1.27, 95% CI: 1.12-1.45, P = 0.000) and homozygous (OR = 1.34, 95% CI:1.04-1.74, P = 0.024) genetic model through random or fixed data pooling method. Both begg's and Egger's line regression test indicated no significant publication bias.ConclusionBased on the present data, there was a significant correlation between MDM2 T309G single nucleotide polymorphism and esophageal cancer susceptibility. Individuals with G genotype may have an increased risk of developing esophageal cancer.
| S-EPMC7049506 | biostudies-literature
Project description:The mouse double minute 2 (MDM2) gene is an important regulator of the p53 suppressor gene. To date, evidence concerning the association of the MDM2 single nucleotide polymorphism (SNP) 309T>G (rs2279744) with the risk of developing oral squamous cell carcinoma (OSCC) remains controversial. Therefore, a meta-analysis of all the eligible studies was performed, in order to derive a more precise estimation of this association. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the degree of association in 5 previous studies, including a total of 1,369 OSCC cases and 2,167 controls. The overall analysis revealed a significant association between MDM2 SNP309 and OSCC risk in the heterozygote (TG vs. TT: OR=0.81; 95% CI: 0.68-0.96; P=0.02) and dominant models (TG+GG vs. TT: OR=0.82; 95% CI: 0.69-0.97; P=0.02). The subgroup analysis based on the source of the controls revealed a significant association between population-based controls and the heterozygote model (TG vs. TT: OR=0.75; 95% CI: 0.62-0.91; P=0.004), dominant model (TG+GG vs. TT: OR=0.76; 95% CI: 0.63-0.91; P=0.003) and allele comparison (G vs. T: OR=0.89; 95% CI: 0.79-0.99; P=0.04). Importantly, no evidence of publication bias or obvious heterogeneity were observed in the meta-analysis. The results of the present study demonstrated a decreased risk of developing OSCC for the MDM2 SNP309 group, suggesting MDM2 SNP309 may be a protection-associated genetic variation for OSCC. Additional well-designed studies, with larger sample sizes, are required to further elucidate this association.
| S-EPMC4906982 | biostudies-literature
Project description:Urinary tract cancer is a common cause of cancer-related death. The etiology and pathogenesis of urinary tract cancer remain unclear, with genetic and epigenetic factors playing an important role. Studies of the polymorphism of murine double minute 2 (MDM2) have shown inconclusive trends in the risk of urinary tract cancer.To clarify this inconsistency, we conducted updated meta-analyses to evaluate the role of MDM2 T309G polymorphism in urinary tract cancer susceptibility.Data sources were Pubmed (1966-May 2015), Chinese biomedicine literature database (1978-May 2015), and hand searching of the reference lists of included studies:(1) research categories case-control study or a nested case-control study; (2) information evaluating the association between the MDM2 SNP309 and urinary tract cancer risk; (3) studies with sufficient data to perform a meta-analysis.It included the use of odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using the funnel plot and the Egger test. Statistical analyses were performed by Review Manage, version 5.0 and Stata 11.0.A total of 18 studies met the eligibility criteria and were included in our analyses. Overall, there was no statistical association between MDM2 SNP309 and prostate cancer risk for the allele contrast, the GG genotype, the recessive genetic model, the dominant genetic model, and prostate cancer risk in all subjects (OR = 0.96, 95% CI 0.87-1.05, P = 0.36; OR = 0.93, 95% CI 0.75-1.15, P = 0.50; OR = 1.00, 95% CI 0.87-1.15, P = 0.99; OR = 0.93, 95% CI 0.80-1.07, P = 0.30), and between MDM2 SNP309 and bladder cancer risk (the allele contrast: OR = 1.06, 95% CI 0.89-1.27, P = 0.50; the GG genotype: OR = 1.12, 95% CI 0.79-1.61, P = 0.52; the dominant genetic model: OR = 1.03, 95% CI 0.83-1.28, P = 0.78; the recessive genetic model: OR = 1.12, 95% CI 0.84-1.49, P = 0.45). However, there was positive association between MDM2 SNP309 and kidney cancer risk for the allele contrast (OR = 1.24, 95% CI 1.05-1.46, P = 0.01), the GG genotype (OR = 1.57, 95% CI 1.11-2.20, P = 0.01), dominant model contrast (OR = 1.30, 95% CI 1.00-1.68, P = 0.05), the recessive genetic model (OR = 1.37, 95% CI 1.02-1.83, P = 0.04).First, only the data of published studies were included in this meta-analysis. Unpublished studies tend to show more negative results; therefore, publication bias may be present. Second, because of the lack of the original data, we did not perform stratification analysis by age, hormone levels, dietary habit, or other variables. This might have caused confounding bias. Third, because the number of studies was relatively small for kidney cancer, the results might not have enough statistical power for us to investigate the association of the polymorphism with kidney cancer susceptibility, and we could not perform subgroup analyses. Finally, there were no studies about Africans in this meta-analysis.In summary, the results of our meta-analysis suggest an increased risk role of the MDM2 SNP T309G in renal cancer. However, there was no association between the MDM2 SNP T309G and prostate cancer risk or between the MDM2 SNP T309G and bladder cancer risk. Moreover, well-designed studies should estimate different ethnicities, degree of malignancy and clinical progression on the association between MDM2 SNP309 and urinary cancer risk in the future.
| S-EPMC4998362 | biostudies-other
Project description:To determine the risk, malignant degree and clinical progression of prostate cancer (PCa) associated with mouse double-minute 2 protein (MDM2) T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk (OR=0.85, 95% CI: 0.74-0.97); this was also the case for the homozygous comparison (OR=0.72, 95% CI: 0.55-0.95) and the dominant genetic model (OR=0.79, 95% CI: 0.65-0.96). The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy (OR=0.85, 95% CI: 0.75-0.96) in the overall analysis, as well as in the heterozygous comparison (OR=0.79, 95% CI: 0.65-0.96), homozygous comparison (OR=0.76, 95% CI: 0.58-0.98) and dominant genetic model (OR=0.81, 95% CI: 0.68-0.96). Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk (OR=0.77, 95% CI: 0.61-0.96); this was also the case in the homozygous comparison (OR=0.51, 95% CI: 0.31-0.86). The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.
| S-EPMC3734987 | biostudies-other
Project description:Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.
| S-EPMC3857251 | biostudies-literature
Project description:Murine double minute clone 2 oncoprotein (MDM2) is a key component in the regulation of the tumour suppressor p53. The association between the MDM2 polymorphism and gastric cancer (GC) has been investigated in Turkish population. In the present case-control study, the aim was to investigate the association between genetic polymorphisms of the MDM2 gene (a major regulator of p53 function) and primary GC risk in a Turkish population. The polymorphism, T309G (rs2279744) in the MDM2 gene was determined in patients with GC (n=65) and in healthy control subjects (n=67) using the polymerase chain reaction-restriction fragment length polymorphism method. The findings were evaluated using logistic regression and χ2 tests. No statistically significant differences were observed between the control subjects and patients with GC regarding smoking status. A comparison between GC cases and control subjects indicated a statistically significant difference for family history of cancer [odds ratio (OR)=0.17; 95% confidence interval (CI), 0.05-0.56; χ2=0.19; P=0.01]. A significant difference was identified in the GG genotype distribution between GC patients and control subjects (OR=4.58; 95% CI, 1.18-17.79; P=0.022). Thus, the results of the present study indicate that the MDM2 gene T309G intron (GG) genotype may be an important risk factor for GC development in the Turkish population.
| S-EPMC5700397 | biostudies-other
Project description:BackgroundMDM2 is a major negative regulator of p53, and a single nucleotide polymorphism (SNP) in the MDM2 promoter region SNP309 has been demonstrated to be associated with an increased MDM2 expression and a significantly earlier age of onset of several tumors, including gastric cancer. Several studies were published to evaluate the association between SNP309 and gastric cancer risk. However, the results remain conflicting rather than conclusive.ObjectiveThe aim of this study was to assess the association between the MDM2 SNP309 polymorphism and gastric risk.MethodsWe performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively.ResultsFive published case-control studies, including 1,621 gastric cancer cases and 2,639 controls were identified. We found that the MDM2 SNP309 polymorphism was associated with a significantly increased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR = 1.54; 95%CI = 1.04-2.29, and GG versus GT/TT, OR = 1.49, 95%CI = 1.30-1.72). Furthermore, Egger's test did not show any evidence of publication bias (P = 0.799 for GG versus TT).ConclusionOur results suggest that the MDM2 SNP309 polymorphism may be a low-penetrant risk factor for the development of gastric cancer.
| S-EPMC3581579 | biostudies-literature
Project description:Preeclampsia (PE) is a hypertensive disorder of pregnancy in which abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role in its pathophysiology. The aim of the current study was to examine the association between Mouse Double Minute 2 (MDM2) T309G and 40 bp insertion/deletion (I/D) polymorphisms and PE risk.A case-control study was conducted on 208 PE women and 164 healthy pregnant women matching age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping.The MDM2 309GG genotype was associated with PE, and this genotype was found to be a risk factor for PE. There was no association between the MDM2 I/D polymorphism and PE. The haplotype-based association analysis revealed no association between MDM2 T309G and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined genotypes were significantly higher in PE women with marginal P values (P = 0.046).The MDM2 309GG genotype was associated with higher risk of PE. The TT-DD and GG-DD combined genotypes were higher in PE women.
| S-EPMC5476551 | biostudies-literature
Project description:BackgroundThe mouse double minute 2 (MDM2) gene encodes a phosphoprotein that interacts with P53 and negatively regulates its activity. The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and colorectal cancer (CRC) risk reported conflicting results. We performed a meta-analysis of all available studies to explore the association of this polymorphism with CRC risk.MethodsAll studies published up to July 2013 on the association between MDM2 SNP309 polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases. The association between the MDM2 SNP309 polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).ResultsA total of 14 case-control studies including 4460 CRC cases and 4828 controls were identified. We did not find a significant association between the MDM2 SNP309 polymorphism and CRC risk in all genetic models in overall population. However, in subgroup analysis by ethnicity, significant associations were found in Asians (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246, 95% CI = 1.106-1.404, P=0.000) and Africans. When stratified by HWE in controls, significantly increased risk was also found among the studies consistent with HWE (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010). In subgroup analysis according to p53 mutation status, and gender, no any significant association was detected.ConclusionsThe present meta-analysis suggests that the MDM2 is a candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk factor for CRC in Asians.
| S-EPMC3786895 | biostudies-literature
Project description:It has been shown that gene polymorphisms may play an important role in the carcinogenesis of esophageal cancer. This study is to investigate the role of alcohol dehydrogenase 1B (ADH1B) gene Arg47His polymorphism in esophageal cancer susceptibility.Case-control studies published between January 2000 and June 2015 were searched to retrieve relevant articles. The pooled odds ratio (OR) and 95 % confidence interval (CI) were employed to calculate the strength of association.A total of 23 relevant articles were finally selected for the analysis, including 9338 esophageal cancer patients and 14,896 matched controls. Overall, we found that the 47His allele was significant associated with the decreased risk of esophageal cancer when compared with the 47Arg allele in total populations (A vs. G: OR?=?0.67, 95 % CI?=?0.59-0.76, P?<?0.00001). This protective relationship was observed under other genetic models as well (P?<?0.00001). Subgroup analysis by ethnicity showed that ADH1B Arg47His variant was associated with the decreased esophageal cancer risk under all the genetic models (P?<?0.00001) among Asians, especially in Chinese and Japanese; while in non-Asians, no significant correlation was detected in any genetic models (P?>?0.05). Furthermore, Arg/Arg genotype of ADH1B Arg47His variant combined with drinking, smoking and males appeared to show a high risk in patients with esophageal cancer.Our results suggested that ADH1B gene Arg47His variant was associated with the decreased esophageal cancer risk. Genetic-environmental interaction should be further considered in the future researches.
| S-EPMC4957421 | biostudies-literature