T309G Polymorphism Research Articles

Are TP53 Arg72Pro and MDM2 T309G polymorphisms associated with bladder cancer risk? A meta-analysis

Background: We still do not know the exact cause of bladder cancer (BC). Objectives: Evaluation of the effect of TP53 Arg72Pro and MDM2 T309G polymorphisms with the risk of Bladder cancer. Methods: A literature search was conducted followed by a meta-analysis. Then, sensitivity and subgroup analyses were performed. 14 relevant studies were included in the quantitative analysis. Results: No statistically significant associations were found. The results of the subgroup analysis revealed a significant association in the Turkish population for T309G: G vs. T (P-value= 0.015; OR 95%CI= 1.51 [1.084; 2.125]), GG vs.TT (P-value= 0.009; OR 95% CI= 2.60 [1.262; 5.370]). Sensitivity analysis revealed a significant association between the Arg72Pro: C vs G (OR= 1.22, 95% CI [1.05; 1.40]), CC vs. GG (OR= 1.54; 95% CI [1.13; 2.09]), CC+CG vs. GG (OR= 1.24; 95% CI [1.01; 1.53]), CC vs. CG+GG (OR= 1.33; 95% CI [1.01; 1.74]), and T309G: G vs. T (OR= 1.30; 95% CI [1.07; 1.57]), GG vs. GT+TT (OR= 1.53; 95% CI [1. 10; 2.11]), GG vs. GT (OR=1.44; 95% CI [1.02; 2.02]), GG vs. TT (OR= 1.88; 95% CI [1.25; 2.82]) with BC occurrence. Conclusion: The T309G polymorphism was found to be a predisposing allele for BC in Turkish population. Keywords: Bladder cancer (BC), polymorphism, Meta-analysis, T309G, Arg72Pro, TP53, MDM2.

Association of MDM2 T309G (rs2279744) Polymorphism and Expression Changes With Risk of Prostate Cancer in the Slovak Population.

The aim of this study was to evaluate the relationship between MDM2 T309G polymorphism and prostate cancer risk in the Slovak population and the association of this polymorphism with MDM2 expression and clinicopathological features. The MDM2 T309G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 506 prostate cancer patients and 592 controls. Quantitative real-time (RT)-PCR and western blot analysis were applied to examine MDM2 expression in 47 prostate cancer tissues and 43 benign prostatic hyperplasia (BPH) tissues. A decreased risk of prostate cancer in men carrying the GG genotype in comparison with the TT genotype was found. A decrease in the relative MDM2 mRNA and protein levels was found in prostate cancer tissues among patients with the MDM2 GG genotype. There is a potentially protective effect of the MDM2 GG genotype on the risk of prostate cancer in the Slovak male population.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background:Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population.Materials and Methods:We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used.Results:A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism.Conclusion:This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population.

Investigation of the association between the MDM2 T309G polymorphism and gastric cancer.

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.

The ID genotype of MDM2 40 bp insertion/deletion polymorphism was associated with lower risk of SLE

BackgroundIn patients with systemic lupus erythematosus (SLE), loss of immunological tolerance to self-nuclear antigens and abnormal activation of self-reactive T and B cells lead to self-antibodies and immune complex production....

The MDM2 promoter T309G polymorphism was associated with preeclampsia susceptibility.

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 40bp 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 40bp 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.

Prevalence of p53 codon 72, p73 G4C14-A4T14 and MDM2 T309G polymorphisms and its association with the risk of oral cancer in South Indians

Background and aimGenetic susceptibility to cancer through single nucleotide polymorphisms - p53 Pro72Arg, p73 G4C14-A4T14 (two linked polymorphism) and MDM2 T309G has been reported in various ethnic populations. Yet the association is unclear in oral cancer of Indian origin where tobacco chewing is widely practiced. The aim of the study was to evaluate the significance of these polymorphisms for the development of oral cancer. Materials and methodsSingle Nucleotide Polymorphisms were genotyped in 204 oral cancer cases and 212 unrelated controls by allele specific polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. ResultsOur results indicate high prevalence of p53 Pro72 [28.92%] in cancer patients and an association with tobacco chewing [OR=3.72, 95%CI=1.697–8.143, p<0.001] as risk habit, while AT variant allele of p73 is less frequent in both the groups [<4%] and the MDM2 polymorphism is equally distributed in cases and control [25.98%] suggesting no involvement in oral cancer. ConclusionWe conclude P53 Proline allele confers risk of developing oral cancer when tobacco chewing is practiced.

Is there a relation between Murine double minute 2 T309G polymorphism and lung cancer risk in the Turkish population?

Abstract Introduction Association between Murine double minute 2 T309G polymorphism and lung cancer risk has been investigated in several populations, but results of these studies are inconsistent. We aimed to investigate the effect of Murine double minute 2 T309G polymorphism on development of lung cancer in a Turkish population. Methods Total 200 subjects including 100 patients and 100 controls were analyzed and used polymerase chain reaction and restriction fragment length polymorphism methods for genotyping analysis of the polymorphism. Results We found that smokers compared with non-smokers have approximately eight fold higher lung cancer risk [p=0.0001, OR=8.27 (4.02–16.9)]. Frequency of GG genotype was higher in patients than in controls, but this ratio was not significant (χ2=3.5, p=0.17). Genotype distribution of the polymorphism was not different neither patients with non-small cell lung cancer nor patients with small cell lung cancer (χ2=2.89, p=0.57). We analyzed together with demographic feature (except smoking habit), clinicopathological findings and genotype frequencies of this polymorphism, and any association with lung cancer risk was not obtained. Conclusion No correlation between Murine double minute 2 T309G polymorphism and lung cancer risk was detected in this Turkish population.

The Relationship Between MDM2 T309G Polymorphism and Leukemia in the Chinese Population: Evidence from a Meta-Analysis.

Increasing numbers of studies have been carried out on the association of MDM2 T309G polymorphism with susceptibility to leukemia and have generated conflicting results. This meta-analysis updated and revaluated the possible associations between MDM2 T309G polymorphism and leukemia in the Chinese population. The PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine were searched up to February 2017. Fixed-effect and random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. Overall, the meta-analysis demonstrated significant associations between the MDM2 T309G polymorphism and increased risk for leukemia in the Chinese population. Subgroup analyses indicated similar results in South China. As for subgroup analysis by clinical types, data suggested increased risk for chronic myeloid leukemia (CML). Our study suggested that MDM2 T309G polymorphism might be a low-penetrant risk factor for leukemia among Chinese.

Relationship Between Murine Double Minute 2 (MDM2) T309G Polymorphism and Endometrial Cancer Risk: A Meta-Analysis.

BackgroundEndometrial cancer is one of the most common cancers in female patients. Many studies have investigated the association between the MDM2 T309G genotype and endometrial cancer incidence, but the results have been inconclusive.Material/MethodsWe performed a systematic search in PubMed and Web of Science databases (update until October 21, 2015) for all English-language publications. The associations are indicated as pooled odds ratio (OR) and 95% confidence intervals (CI).ResultsWe identified 8 relevant publications (9 case-control studies), including 2188 cases and 4654 controls, that assessed the relationship between MDM2 T309G polymorphism and endometrial cancer risk. There was a significant association between MDM2 T309G polymorphism and endometrial cancer risk in the overall population in the recessive model (OR=1.61; 95% CI: 1.19–2.19; P=0.002). In the subgroup of different ethnic populations, the subgroup analysis showed MDM2 T309G polymorphism was significantly associated with increased endometrial cancer risk in Caucasians (OR=1.75; 95% CI: 1.16–2.63; P=0.007). No similar result was found in Asians.ConclusionsOur meta-analysis provides evidence that MDM2 T309G polymorphism is associated with endometrial cancer, especially in Caucasians.

Association between XRCC1 ARG399GLN, TP53 ARG72PRO and MDM2 T309G polymorphisms and the risk of breast cancer in women of the Kyrgyz population

Aim. To study an association between Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene polymorphisms and breast cancer (BC) rate in women of the Kyrgyz population Material and Methods. Genomic DNA was obtainedfrom the whole blood of 117 breast cancer patients and 102 cancer-free healthy women residing in the Kyrgyz Republic. XRCC1 (Arg399Gln), TP53(Arg72Pro) and MDM2 (T309G) genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. Results. Women with the 399Gln allele had 1,57 fold higher risk (OR=1,57; p=0,034) of developing breast cancer than cases without these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2,77 fold higher risk (OR=2,77; p=0,0010) of BC. Notably, haplotype analyses revealed a stronger association with breast cancer risk if compare with data of the genotype analysis at each locus alone. The combination of heterozygous XRCC1 (Arg399Gln) variant and TP53 (Arg72Pro) genes increased even more the risk of BC (OR=3,98; p=0,0059). The combination of Arg399Gln and T309G genotypes of - XRCC1 and MDM2 genes is significant association with risk of BC (OR=3,0; p=0,034). We showed the combinations of Arg399Gln, Arg72Pro and T309Ggenotypes of-XRCC1, TP53 andMDM2 genes is related to the strong association with risk of BC in Kyrgyz women (OR=6,40; p=0,025). Conclusion. The polymorphisms Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene are associated with an increased risk of BC in Kyrgyz females. Combinations of unfavorable genotypes of several candidate genes increase even more the risk of BC.

Association of MDM2 promoter T309G polymorphism with oral cancer risk: A meta-analysis of 3,536 subjects.

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.

Is MDM2 SNP309 Variation a Risk Factor for Head and Neck Carcinoma?

Murine double minute-2 (MDM2) is a negative regulator of P53, and its T309G polymorphism has been suggested as a risk factor for a variety of cancers. Increasing evidence has shown the association of MDM2 T309G polymorphism with head and neck carcinoma (HNC) risk. However, the results are inconsistent. Thus, we performed a meta-analysis to elucidate the association.The meta-analysis retrieved studies published up to August 2015, and essential information was extracted for analysis. Separate analyses on ethnicity, source of controls, sample size, detection method, and cancer types were also conducted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate the association.Pooled data from 16 case–control studies including 4625 cases and 6927 controls failed to indicate a significant association. However, in the subgroup analysis of sample sizes, an increased risk was observed in the largest sample size group (>1000) under a recessive model (OR = 1.52; 95% CI = 1.08–2.13). Increased risks were also found in the nasopharyngeal cancer in the subgroup analysis of cancer types (GG vs TT: OR = 2.07; 95% CI = 1.38–3.12; dominant model: OR = 1.48; 95% CI = 1.13–1.93; recessive model: OR = 1.76; 95% CI = 1.17–2.65).The results suggest that homozygote GG alleles of MDM2 SNP309 may be a low-penetrant risk factor for HNC, and G allele may confer nasopharyngeal cancer susceptibility.

Murine Double Minute 2 SNP T309G Polymorphism and Urinary Tract Cancer Risk: A Meta-Analysis.

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 I2 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.

P53 R72P Alone and in Combination with MDM2 SNP T309G is Associated with Colon Carcinoma Incidence and Survival

Introduction: Protein p53 is encoded by tumor suppressor TP53, which regulates key cellular functions such as transcription, cell cycle arrest, DNA repair and apoptosis. Murine double minute 2 homolog (MDM2), a p53 transcribed protein, negatively regulates p53. A single nucleotide polymorphism (SNP) at codon 72 of TP53 (R72P, rs rs1042522) alters an amino acid, while an SNP T309G (rs2279744) polymorphism (SNPT309G) in the promoter region of MDM2 has been reported to modulate its transcription. p53 R72P and MDM2 SNPT309G have been reported to associate alone and or in combination with various carcinomas. In this study, we aimed to determine if p53 R72P and MDM2 SNPT309G polymorphism alone or in combination are associated with colon carcinoma incidence, tumor progression and/or patient survival in Swedish population. Materials and methods: We determined polymorphisms in 151 colon carcinoma patients and 188 healthy controls by PCR-Pyrosequencing. For statistical analysis, we applied logistic regression analysis, Chi square and multivariate Cox regression to determine incidence, progression of colon carcinoma and overall patient survival respectively. Statistical analyses were two sided. Results: We found that individual carriers of Arg/Pro and Pro/Pro+Pro/Arg (Pro/--) are at 1.72 (95% CI; 1.09-2.72), and 1.659(95% CI; 1.07-2.58) fold higher risk of developing colon carcinoma compared to the carriers of Arg/Arg individuals. We did not find association of MDM2 SNPT309G with incidence of colon carcinoma. No association was found between p53 and MDM2 polymorphisms and clinicopathological parameters, except for TT variant that was correlated with low-differentiated tumors. We also found that people with Arg/Pro and Pro/--- had significantly lower overall survival compared with the people having Arg/Arg variants (Arg/Pro, OR; 1.75, 95% CI; 1.09-2.75, Pro/---, OR; 1.7, 95% CI; 1.065-2.68), but MDM2 polymorphism was not associated with patient survival. In combined analysis, with reference to Arg/Arg+TG/GG, Pro/---+TG/GG was marginally correlated with colon carcinoma incidence (OR; 1.75, 95% CI; 0.99-3.11), while Pro/---+TT was significantly correlated with poor patient survival (OR; 2.03, 95% CI; 1.029-4.02). Conclusion: p53 R72P polymorphism is associated with the incidence of colon carcinoma and patient survival. p53 and MDM2 polymorphism appear to interact with each other and modify the association with colon carcinoma incidence and patients’ survival.

ASSOCIATION BETWEEN MURINE DOUBLE MINUTE 2 - T309G polymorphism and recurrence of hepatocellular carcinoma after surgical treatment.

Discovery and incorporation of biomarker panels to cancer studies enabled the understanding of genetic variation and its interference in carcinogenesis at molecular level. The potential association between single nucleotide polymorphism (SNP) 309 and increased development of tumors, such as hepatocellular carcinoma, has been subject to several studies. This is the first study on this association conducted in Brazil. 62 cases of cirrhotic patients with hepatocellular carcinoma surgically treated by partial hepatectomy (HPT) or by liver transplantation (LTX) from 2000 to 2009 at Santa Casa Hospital Complex, in the city of Porto Alegre, were retrospectively analyzed. Tumor samples from surgical specimen were collected and prepared for study in paraffin blocks. Overall survival was 26.7 months in the HPT group and 62.4 months in the LTX group (P <0.01). Overall tumor recurrence was 66.7% in the HPT group (10/15) and 17% in the LTX group (8/47) (X²=13.602, P <0.01). Alpha-fetoprotein levels >200ng/mL, microvascular invasion and histological grade were associated with tumor recurrence (P <0.01). Recurrence rates in each surgical group and analysis of factors associated with tumor recurrence, when stratified for each genotypic pattern, were both not statistically significant. G/G genotype was not associated with tumor recurrence after surgical treatment and it did not show any correlation with other prognostic factors.

Clinical significance of TP53 (R72P) and MDM2 (T309G) polymorphisms in breast cancer patients.

TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients. The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects. It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (χ (2)=9.92, p=0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95% CI: 1.22-2.77), risk ratio 1.34 (95% CI: 1.11-1.63), p value 0.003], HER2/neu status (p=0.01) and distant metastasis (p=0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2)=11.14, p=0.003) and distant metastasis (p value=0.04). Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53.

Association of MDM2 Polymorphism with Risk and Prognosis of Leukemia: A Meta-Analysis

Objective: In this study, we performed an updated meta-analysis by summarizing all available relevant association studies to evaluate whether the murine double minute-2 (MDM2) T309G polymorphism is associated with risk of leukemia and to determine its prognostic effect. Material and Methods: Studies published in PubMed, Embase and the Cochrane Controlled Trial Register were searched till June 2014 using the search terms ‘MDM2', ‘polymorphism' and ‘leukemia'. Results: Eleven studies were included in this meta-analysis, with a total of 2,478 patients accrued. There were 8 studies providing data on single nucleotide polymorphism at position 309 (SNP309) and risk of leukemia and 7 studies providing data on SNP309 and overall survival. Our analysis showed that patients having G/G mutations had a significantly higher risk of developing leukemia (HR 1.90, 95% CI 1.56-2.31, p < 0.00001), while the association between G/T and leukemia was not significant (HR 1.18, 95% CI 0.96-1.45, p = 0.11). In addition, SNP309 was not significantly associated with patient survival (HR 1.29, 95% CI 0.79-2.13, p = 0.31). Conclusions: Our meta-analysis showed that the MDM2 T309G variation, especially homozygous G/G, might be associated with an increased risk of leukemia. Additional studies are needed to confirm the findings as well as to understand the underlying mechanisms.

Age-dependent association of MDM2 promoter polymorphisms and uterine leiomyoma in South-East Iran: A preliminary report.

Murine double minute clone 2 (MDM2) is an important regulator of p53 tumor suppressor protein. Because increased MDM2 expression has been observed in different tumors, its polymorphisms are proposed to be associated with accelerated tumor formation. The aim of this study was to examine the association between T309G (rs2279744) and 40-bp Insertion/deletion (rs3730485) polymorphisms of the MDM2 gene and risk of uterine leiomyoma (UL). We analyzed the MDM2 gene polymorphisms of 154 UL patients and 197 healthy controls by polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism (RFLP) methods. The frequency of MDM2 T309G polymorphism genotypes was not different between UL women and controls. Although there was an association between MDM2 40-bp del/del genotype and UL before and after adjustment for age, the association between Insertion/deletion (Indel) genotype and UL was significant after adjustment for age. MDM2 T309G polymorphism was not associated with UL and MDM2 40-bp Indel polymorphism could be an age-related risk factor for UL.

Polymorphisms in the Apoptosis Pathway in Cutaneous Melanoma: Recurrence and Survival

ABSTRACT Aim: Cutaneous melanoma (CM) is notorious for its poor prognosis and resistance to conventional chemotherapy. Genes involved in the apoptosis pathway, such as P53, (tumor suppressor gene), MDM2 (p53 inhibitor), BAX (proapoptotic) and BCL2 (anti-apoptotic) are important for CM growth and survival. The aim of this study was to evaluate whether P53 Arg72Pro, MDM2 T309G, BAX G(-248)A and BCL2 C(-938)A polymorphisms, involved with inherited variations in apoptosis, are associated with relapse free survival (RFS) and overall survival (OS) of CM patients. Methods: Our analysis included 234 consecutive CM patients at diagnosis seen at our University Hospital from December 1989 to November 2013. Genomic DNA from peripheral blood of patients was analyzed by polymerase chain reaction followed by enzymatic digestion for discrimination of pertinent genotypes. RFS and OS were calculated using the univariate Kaplan-Meier estimate probabilities, and differences between survival curves were analysed by the log-rank test. RFS was defined as the time to beginning of treatment until the date of the first relapse. OS was calculated from date of first diagnosis until the date of death or last follow-up. Results: The median period of observation of patients in study was 50 months (9-192) for RFS and 58 months (range: 9-285) for OS. We observed at 120 months of segment, that the RFS was higher in patients with BCL2 CC + CA plus MDM2 TT + TG than patients with BCL2 AA plus MDM2 GG genotypes (54% versus 37%, P = 0.01). The OS in CM patients with the BAX GA + AA was higher than in those with the GG genotypes (100% versus 80%, P = 0.01). Moreover, the OS was also higher in patients with BAX GA + AA plus BCL2 CC + CA combined genotype than in those with BAX GG plus BCL2 AA (100% versus 78%, P = 0.02) and BAX GA + AA plus MDM2 TT + TG than BAX GG plus MDM2 GG (100% versus 71%, P = 0.001). Conclusions: The data suggest, for the first time, that BAX G(-248)A polymorphism may independent or jointly with BCL2 C(-938)A and MDM2 T309G polymorphisms modulate RFS and OS in CM patients. Additional studies will provide some promising guidance for clinical management and tailored or personalized therapeutics in treating for CM. Disclosure: All authors have declared no conflicts of interest.