The MDM2 SNP309T>G Polymorphism Increases Bladder Cancer Risk among Caucasians: a Meta-analysis

Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with thecorresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for therecessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.     

Polymorphisms in the MDM2 gene and risk of malignant bone tumors: a meta-analysis

There are several studies published to assess the associations of murine double minute 2 (MDM2) genetic polymorphisms with risk of malignant bone tumors, but they reported contradictory results and failed to confirm a strong and consistent association. To assess the evidence regarding the associations of MDM2 genetic polymorphisms with the risk of malignant bone tumors, we conducted a meta-analysis of epidemiological studies. The pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) was used to assess these possible associations. Four studies with a total of 3,958 individuals were finally included the meta-analysis. Meta-analysis of two studies on MDM2 SNP309 polymorphism showed that MDM2 SNP309 polymorphism was associated with an increased risk of malignant bone tumors (G versus T: OR?=?1.72, 95 % CI 1.35–2.20, P?<?0.001; GG versus TT: OR?=?2.64, 95 % CI 1.59–4.39, P?<?0.001; GG/GT versus TT: OR?=?1.87, 95 % CI 1.33–2.62, P?<?0.001; GG versus TT/GT: OR?=?2.20, 95 % CI 1.38–3.51, P?=?0.001). Meta-analysis of those two studies on MDM2 rs1690916 polymorphism showed that MDM2 rs1690916 minor allele A was associated with decreased risk of malignant bone tumors (OR?=?0.60, 95 % CI 0.46–0.77, P?<?0.001). Meta-analyses of available data show that there are significant associations of MDM2 SNP309 polymorphism and MDM2 rs1690916 polymorphism with malignant bone tumors.     

Association between the MDM2 T309G Polymorphism and Leukemia Risk: a Meta-analysis

Several studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and leukemia risk, but they reported contradictory results. For better understanding of the effect of MDM2 T309G polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature (CBM) databases before May 2014. Assessment of associations between the MDM2 T309G polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of 11 publications covering 12 case-control studies with 2, 362 cases and 5, 562 controls concerning MDM2 T309G polymorphism with respect to leukemia were included in the meta-analysis. Significant associations were found between MDM2 T309G polymorphism and leukemia risk in four models in overall populations (G vs T: OR=1.29, 95% CI=1.11-1.49, p=0.001; GG vs TT: OR=1.67, 95% CI=1.21-2.30, p=0.002; GG vs TG/TT: OR=1.56, 95% CI=1.21-2.00,p=0.001; GG/TG vs TT: OR=1.28, 95% CI=1.05-1.57, p=0.015). In the sub-group analysis according to ethnicity, increased leukemia risks were observed in three genetic models among Asians but not Caucasians. In conclusion, the results of our meta-analysis suggest that the MDM2 T309G polymorphism can increase the risk of leukemia, especially among Asian populations.     

Meta-analysis of the MDM2 T309G Polymorphism and Gastric Cancer Risk

Background: Mdm2 binds to the amino-terminus of p53 to induce its degradation and a single nucleotidepolymorphism in the MDM2 promoter region (T309G) has been reported to increase the risk of several carcinomas,such as gastric cancer. However, the results of published studies to analyze the association between MDM2 T309Gand gastric cancer havve often conflicted. Methods: To better illustrate the filiation between MDM2 T309G andgastric cancer, we performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were usedto evaluate the strength of the relationship. The pooled ORs were performed for 4 models, additive, recessive,co-dominant model, and dominant. Results: Nine published case-control studies including 3,225 gastric cancercases and 4,118 controls were identified. The MDM2 T309G polymorphism was associated with a significantlyincreased risk of gastric cancer risk when all studies were pooled into the meta-analysis (GG versus TT, OR=1.57;95%CI=1.57-2.12; p=0.003) and GG versus GT/TT, OR=1.52; 95%CI=1.217-1.90; p<0.001). Furthermore, Egger’stest did not show any evidence of publication bias (P = 0.608 for GG versus TT). Conclusion: Our results suggestthat the MDM2 T309G polymorphism is indeed associated with a significantly increased risk of gastric cancer.     

Meta-analysis of Associations between the MDM2-T309G Polymorphism and Prostate Cancer Risk

The mouse double minute 2 (MDM2) gene plays a key role in the p53 pathway, and the SNP 309T/G singlenucleotidepolymorphism in the promoter region of MDM2 has been shown to be associated with increased riskof cancer. However, no consistent results were found concerning the relationships between the polymorphismand prostate cancer risk. This meta-analysis, covering 4 independent case-control studies, was conducted tobetter understand the association between MDM2-SNP T309G and prostate cancer risk focusing on overall andsubgroup aspects. The analysis revealed, no matter what kind of genetic model was used, no significant associationbetween MDM2-SNP T309G and prostate cancer risk in overall analysis (GT/TT: OR = 0.84, 95%CI = 0.60-1.19;GG/TT: OR = 0.69, 95%CI = 0.43-1.11; dominant model: OR = 0.81, 95%CI= 0.58-1.13; recessive model: OR =1.23, 95%CI = 0.95-1.59). In subgroup analysis, the polymorphism seemed more likely to be a protective factorin Europeans (GG/TT: OR = 0.52, 95%CI = 0.31-0.87; recessive model: OR = 0.58, 95%CI = 0.36-0.95) thanin Asian populations, and a protective effect of the polymorphism was also seen in hospital-based studies in allmodels (GT/TT: OR = 0.74, 95%CI = 0.57-0.97; GG/TT: OR = 0.55, 95%CI = 0.38-0.79; dominant model: OR= 0.69, 95%CI = 0.54-0.89; recessive model: OR = 0.70, 95%CI = 0.51-0.97). However, more primary studieswith a larger number of samples are required to confirm our findings.     

MDM2 promoter SNP309 is associated with risk of occurrence and advanced lymph node metastasis of nasopharyngeal carcinoma in Chinese population.

PURPOSE: Mouse double minute 2 (MDM2) is a key negative regulator of the p53 activity. Recently, a polymorphism in the MDM2 intronic promoter, SNP309, was shown to influence MDM2 expression and p53 activity. We examined whether the SNP309 was related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. EXPERIMENTAL DESIGN: We genotyped the SNP309 in two independent case-control populations in southern China, one is from Guangxi province (including 593 NPC patients and 480 controls) and the other is from Guangdong province (including 239 patients and 286 controls), by PCR direct sequencing. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: We observed that compared with the TT genotype, the genotypes containing G allele (GT + GG genotype) were associated with significant increased susceptibility to NPC in both Guangxi (OR, 1.43; 95% CI, 1.04-1.91) and Guangdong population (OR, 1.53; 95% CI, 1.00-2.36). When these two sample sets were combined, the OR of the GT + GG genotype developing NPC was 1.45 (95% CI, 1.12-1.85) compared with the TT genotype. Furthermore, compared with the TT genotype, the GT + GG genotype was also significantly associated with the advanced lymph node metastasis (OR, 1.84; 95% CI, 1.09-3.05). CONCLUSIONS: Our findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of NPC in Chinese population.     

Murine double minute 2 rs2279744 polymorphism and hepatocellular carcinoma risk in East Asians: a meta-analysis

Murine double minute 2 (MDM2) is a crucial negative regulator of p53 function through several mechanisms. There are many studies performed to assess the association between MDM2 rs2279744 polymorphism and hepatocellular carcinoma risk, but the impact of MDM2 rs2279744 polymorphism on hepatocellular carcinoma in East Asians is unclear owing to the inconsistent findings from previous studies. We conducted a comprehensive meta-analysis of epidemiological studies to shed some light on these contradicting results. We used pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to assess the association. Overall, seven studies with a total of 4,993 subjects were finally included. The meta-analysis suggested that MDM2 rs2279744 polymorphism was significantly associated with increased risk of hepatocellular carcinoma in East Asians (G versus T: OR?=?1.27, 95 % CI 1.06–1.52, P?=?0.01; GG versus TT: OR?=?1.59, 95 % CI 1.11–2.27, P?=?0.01; GG/GT versus TT: OR?=?1.41, 95 % CI 1.07–1.87, P?=?0.02; GG versus TT/GT: OR?=?1.32, 95 % CI 1.08–1.62, P?=?0.008). Sensitivity analysis by excluding low-quality study still suggested that the association above was still significant. Thus, the findings from the meta-analysis support that MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians.     

MDM2 SNP309 variation increases cervical cancer risk among Asians

MDM2 T309G polymorphism has been suggested to be a risk factor for a number of cancers. The association of MDM2 T309G genetic variation with cervical cancer risk remains inconclusive. In the present study, we aimed to get a more confidential result by conducting a quantitative meta-analysis. Relevant literature up to October 2013 was searched and screened. Essential information was rigorously extracted for data pooling and analyzing, and then, separate analyses on ethnicity and source of controls were also performed. As a result, four articles including five case–control studies were selected. The overall data failed to show a significant association between MDM2 T309G polymorphism and cervical cancer risk (GG vs TT: odds ratio (OR)?=?1.31; 95 % confidence interval (CI)?=?0.55–3.13; dominant model: OR?=?1.22; 95 % CI?=?0.65–2.31; recessive model: OR?=?1.45; 95 % CI?=?0.79–2.65). However, in the subgroup analysis about ethnicity, increased cancer risk could be shown among Asians (GG vs TT: OR?=?2.15; 95 % CI?=?1.03–4.51; recessive model: OR?=?2.01; 95 % CI?=?1.32–3.06). In conclusion, the results of the present study suggest that homozygous GG alleles of MDM2 T309G polymorphism might be a risk factor for cervical cancer among Asians. Further studies are needed get a more definitive conclusion.     

MDM2 SNP309 variation contributes to leukemia risk: meta-analyses based on 7259 subjects

Abstract Evidence implicates MDM2 (murine double minute-2) T309G polymorphism as a risk factor for several cancers. Increasing numbers of studies have been carried out on the association of MDM2 T309G polymorphism with susceptibility to leukemia and have generated conflicting results. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses assessing the association of MDM2 T309G variation with leukemia were conducted. Separate analyses on ethnicity and clinical types were also performed. Eligible studies were identified for the period up to February 2012. Consequently, seven publications including eight case-control studies with 1777 cases and 5482 controls were selected for analysis. The overall data indicated a significant association of the MDM2 T309G polymorphism with leukemia risk (GG vs. TT: odds ratio [OR] =?1.62; 95% confidence interval [CI] =?1.14-2.29; dominant model: OR =?1.20; 95% CI =?1.06-1.36; recessive model: OR =?1.47; 95% CI =?1.07-2.03). In subgroup analysis by ethnicity, the G allele may increase leukemia susceptibility among Asians (GG vs. TT: OR =?3.06; 95% CI =?2.05-4.56; dominant model: OR =?1.82; 95% CI =?1.31-2.51; recessive model: OR =?2.32; 95% CI =?1.69-3.19) but not Caucasians. In subgroup analysis by clinical types, data suggested increased risk for acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) under additive and recessive models, respectively. Similarly, elevated risk for chronic lymphocytic leukemia (CLL) was shown under the dominant model. Collectively, the results of the present study suggest that MDM2 T309G polymorphism might be a low-penetrant risk factor for leukemia among Asians but not Caucasians. The G allele might increase CLL susceptibility and homozygous GG might elevate AML and CML risk.     

Involvement of p53 R72P polymorphism in the association of MDM2-SNP309 with breast cancer

The allelic variant MDM2-SNP309 (T>G) has been suggested to influence cancer development, but the clinical correlation between the risk allele and breast cancer remains controversial. The genetic background and the ethnicity of selected subgroups may influence the power of these risk genotypes. In this study, we investigated whether MDM2-SNP309 is associated with p53 R72P genetic polymorphism for the risk of breast cancer development in Asian Taiwanese, which has not been well-studied in this regard. Two hundred and fifty-five patients and 324 cancer-free controls were included, and we found that the MDM2-SNP309 TG and GG genotypes displayed marginally increased risks of breast cancer (GG vs. TT: OR = 1.7, 95% CI = 0.93 to 3.09; TG + TT vs. TT: OR = 1.57, 95% CI = 0.98 to 2.56). The breast cancer risk associated with MDM2-SNP309 was enhanced after stratification for the homozygous GG genotype at p53 codon 72 representing the Arg form of this genotype (GG vs. TT: OR = 3.7, 95% CI = 1.144 to 12.02; TG + GG vs. TT: OR = 2.7, 95% CI = 1.027 to 6.895). Also, the median age at diagnosis of patients with MDM2-SNP309 GG increased from 4 years earlier to 9 years earlier than TT patients after stratification for the GG genotype at p53 codon 72. Moreover, the G-allele of MDM2-SNP309 exhibited a stronger capacity than the T-allele to drive the full-length P2 promoter of the MDM2 gene in several human cell lines, suggesting that the association between MDM2-SNP309 and breast cancer is likely multifactorial rather than due to inconsistent gene expression in different cancer sources.     

Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck

Both p53 tumor suppressor and murine double minute 2 (MDM2) oncoprotein are crucial in carcinogenesis. We hypothesized that MDM2 promoter single nucleotide polymorphisms (SNPs) SNP309 T > G, A2164G, and p53 codon 72 are associated with risk and age at onset of squamous cell carcinoma of head and neck (SCCHN). We genotyped these SNPs in a study of 1,083 Caucasian SCCHN cases and 1,090 cancer-free controls. Although none of these SNPs individually had a significant effect on risk of SCCHN, nor did their combined putative risk genotypes (i.e., MDM2 SNP309 GT + GG, 2164 AA, and p53 codon 72 CC), we found that individuals with two to three risk genotypes had significantly increased risk of non-oropharyngeal cancer (OR = 1.42; 95% CI = 1.07-1.88). This increased risk was more pronounced among young subjects, men, smokers, and drinkers. In addition, female patients carrying the MDM2 SNP309 GT and GG genotypes showed a 3-yr (56.7 yr) and 9-yr (51.2 yr) earlier age at onset of non-oropharyngeal cancer (P(trend) = 0.007), respectively, compared with those carrying the TT genotype (60.1 yr). The youngest age (42.5 yr) at onset of non-oropharyngeal cancer was observed in female patients with the combined MDM2 SNP309 GG and p53 codon 72 CC genotypes. The findings suggest that MDM2 SNP309, A2164G, and p53 codon 72 SNPs may collectively contribute to non-oropharyngeal cancer risk and that MDM2 SNP309 individually or in combination with p53 codon 72 may accelerate the development of non-oropharyngeal cancer in women. Further studies with large sample sizes are warranted to validate these results.     

MDM2 SNP309 and cancer risk: a combined analysis

A paper by Bond et al. reported that a single-nucleotide polymorphism (SNP) in the intronic promoter region of the mouse double minute 2 (MDM2) gene (called SNP309) can significantly change the expression of MDM2 and thereby suppress the p53 pathway. Furthermore, it was shown that SNP309 accelerates tumor formation in Li-Fraumeni patients. This initial report aroused the attention of many researchers, which investigated the role of SNP309 for the risk and the onset of cancer in different tissues. To provide a more robust estimate of the effect of this polymorphism on cancer risk, we combined the available genotype data for breast, colorectal and lung cancers. For breast cancer, we combined the data from 11 studies including 5737 cases and 6703 controls. For colorectal cancer, we combined the data from five studies with 1620 cases and 886 controls. For lung cancer, we performed a fixed-effect meta-analysis from seven studies including 4276 cases and 5318 controls. Our results suggest that the SNP309 variant does not have an impact on the risk of breast [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.87-1.08] or colorectal cancers (OR = 0.97, 95% CI = 0.76-1.25). However, the combined estimate of the ORs for lung cancer revealed an increased risk for GG versus TT (OR = 1.27, 95% CI = 1.12-1.44). The data show that SNP309 alone has little or no effect on the risk of common cancers, but it might modify the time of tumor onset and prognosis.     

MDM2 启动子区309 位点基因多态性与乳腺癌风险的关系*

目的:采用病例- 对照研究检测MDM2 启动子区309 位点T>G 单核苷酸多态（SNP 309）在中国女性人群中的频率分布,分析其与中国女性乳腺癌发病风险的关系。方法:提取病例组698 例原发性乳腺癌患者及对照组525 例健康人的外周血单核细胞DNA,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）分析法,检测MDM2 启动子区309 位点基因多态性,确定此位点三种基因型,即T/T、T/G、G/G 基因型。统计分析病例组和对照组人群MDM2 SNP 309 各基因型频率分布,及各基因型与乳腺癌发病风险的相关性。结果:在研究的病例组与对照组整体人群中,经年龄、月经状态、家族史及生育史等因素校正后,与MDM2 SNP 309 T/T基因型比较,T/G 型及G/G 型与乳腺癌的发病风险无显著相关性（T/G,adjusted OR= 1.2,95%CI:0.8～1.6,P=0.30;G/G,adjusted OR= 1.0,95%CI:0.7～1.5,P=0.88）。 进一步分层分析后显示:在绝经后人群中,与T/T基因型比较,T/G 基因型及G/G 基因型显著增加乳腺癌的发病风险（T/G,adjusted OR= 1.8,95%CI:1.2～3.0,P=0.011;G/G,adjusted OR= 1.9,95%CI:1.2～3.3,P=0.014）。 提示绝经后人群携带T/G 型、G/G 型者比携带T/T基因型者患乳腺癌的风险分别升高约1.8、1.9 倍。在绝经前人群中,各基因型与乳腺癌的发病风险无显著相关性（P>0.05）。 结论:MDM2 启动子309 位点突变型G 等位基因携带者显著增加绝经后女性乳腺癌的发病风险。      

Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study

Background: Genetic factors play a substantial role in acute myeloid leukemia (AML) etiology. Overexpression of the mouse double minute 2 (MDM2) gene has been explored in many tumors. However, the role of MDM2 -309T>G (rs2279744) polymorphism in AML remains unclear. We have performed this study to examine the association of MDM2 -309T>G with AML in an Iranian population. Methods: We have examined the association of N MDM2 -309T>G polymorphism in 73 cases diagnosed with AML and 80 healthy controls by tetra-primer amplification refractory mutation system (ARMS) PCR assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. Results: The TT, GG and GG genotypes of MDM2 -309T>G polymorphism in patients were 32.9%, 23.2% and 43.9%, while in controls were 86.2%, 7.5% and 6.3%, respectively. Moreover, Frequency of mutant allele (G) was 55.6% in cases with AML and 10.0% in controls. The mutant homozygote genotype (GG) was associated with an increased susceptibility to AML (OR 1.471; 95% CI: 1.062-1.844; p=0.004). Conclusion: Our results showed that the MDM2 -309T>G polymorphism was significantly associated with increased risk of AML in the Iranian population. Thus, the MDM2 -309T>G polymorphism might be useful genetic susceptibility factors in the pathogenesis of AML.     

The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma

The tumor suppressor P53 pathway plays a crucial role in preventing carcinogenesis and genetic variations of this pathway may be associated with cancer susceptibility. We tested this hypothesis by examining the contribution of functional polymorphisms in P53 and MDM2 to risk of esophageal squamous cell carcinoma (ESCC). DNA from 758 ESCC patients and 1,420 controls were genotyped for P53 codon 72Arg>Pro and MDM2 309T>G polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) of ESCC were estimated by logistic regression. We observed an increased risk of ESCC associated with the P53 Pro/Pro (OR, 1.83; 95% CI, 1.43-2.35; P < 0.001) or MDM2 GG (OR, 1.49; 95% CI, 1.16-1.91; P = 0.002) genotype, compared with the P53 Arg/Arg or MDM2 TT genotype, respectively. Interaction between these P53 and MDM2 polymorphisms increased risk of ESCC in a multiplicative manner, with the OR being 3.10 (95% CI, 2.07-4.69) for subjects carrying both P53 Pro/Pro and MDM2 GG genotypes. Significant interactions were observed between these polymorphisms and smoking, with risk being the highest (OR, 5.29; 95% CI, 2.91-9.61) in smokers having both P53 Pro/Pro and MDM2 GG genotypes. The MDM2 GG genotype was also associated with risk of developing poorly differentiated and advanced ESCC compared with the GT or TT genotype (OR for high-grade and stages III-IV versus low-grade and stages I-II = 1.60; 95% CI, 1.00-2.64; P = 0.049). The P53 and MDM2 polymorphisms may be genetic determinants for the development of ESCC.     

MDM2基因SNP309多态性与宫颈癌的相关性研究

目的：研究汉族妇女中MDM2基因SNP309多态性与宫颈癌易感性及临床病理学参数之间的关系。方法：用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA, 其中宫颈癌患者105例, 正常对照组140例; 用聚合酶链式反应-限制性片段长度多态 （PCR-RFLP） 和直接测序方法测定MDM2-SNP309单核苷酸多态基因型。结果：宫颈癌患者的MDM-SNP309 G等位基因频率显著高于对照组 （60.0% vs 48.6%, P=0.012; OR=1.59, 95% CI=1.11～2.28）; 宫颈癌与对照组之间的GG、 TG和TT等位基因型的分布差异有统计学意义, 其中GG等位基因型在宫颈细胞癌中的频率显著高于对照组 （36.2% vs 18.6%, P=0.016; OR=2.58,95% CI=1.19～5.61）。在宫颈癌组中, 淋巴转移阳性组MDM2-SNP309 GG等位基因型显著高于淋巴转移阴性组 （31.8% vs 11.5%, P<0.05）, SNP309单核苷酸多态性分布与肿瘤组织学类型、病理分级及肿瘤大小无关。结论:MDM2基因SNP309 GG基因型是宫颈癌发生的遗传易感因素, 与宫颈癌的淋巴转移发生有相关性。     

The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians

MDM2 plays a key role in modulating p53 function. The MDM2 SNP309T > G promoter polymorphism enhances Sp1 binding and has been linked to cancer risk and young age at diagnosis although with conflicting evidence. We report a second MDM2 promoter polymorphism, SNP285G > C, residing on the SNP309G allele. SNP285C occurs in Caucasians only, where 7.7% (95% CI 7.6%-7.8%) of healthy individuals carry the SNP285C/309G haplotype. In?vitro analyses reveals that SNP309G enhances but SNP285C strongly reduces Sp1 promoter binding. Comparing MDM2 promoter status among different cohorts of ovarian (n?= 1993) and breast (n?= 1973) cancer patients versus healthy controls (n?= 3646), SNP285C reduced the risk of both ovarian (OR 0.74; CI 0.58-0.94) and breast cancer (OR 0.79; CI 0.62-1.00) among SNP309G carriers.     

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 beenreported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutationsin p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphismon breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an associationbetween 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 reactionand restriction length fragment polymorphism methods were used. Results: A significant difference was observedbetween case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). Therewas 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 riskfactors for breast cancer in our Turkish population.     

Association Between Three eNOS Polymorphisms and Cancer Risk: a Meta-analysis

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of cancer, but the results are still debatable. Therefore, we performed a systematic review to provide a more complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, EMBASE, EBSCO, Google Scholar and China National Knowledge Infrastructure (CNKI) databases until April 2014 to identify eligible studies. Thirty-one studies with cancer patients and controls were included in the meta-analysis. Overall, thepolled analysis revealed that the T-786C polymorphism was significantly associated with increased cancer risk under multiple genetic models (C vs T: OR=1.135, 95%CI=1.048-1.228; CC vs TT: OR=1.278, 95%CI=1.045-1.562; TC vsTT: OR=1.136, 95%CI=1.023-1.261; CC+TC vs TT: OR=1.159, 95%CI=1.047-1.281; CC vs TC+TT: OR=1.204, 95%CI= 1.003-1.447). G894T was associated with significant risk for females (TT vs GG: OR=1.414, 95%CI=1.056-1.892; TT vs GT+GG: OR=1.356, 95%CI=1.108-1.661) and for breast cancer (T vs G: OR=1.097, 95%CI=1.001-1.203; TT vs GG: OR=1.346, 95%CI=1.012-1.789; TT vs GT+GG: OR=1.269, 95%CI=1.028-1.566). Increased susceptibility was revealed for prostate cancer with 4a/b (ba vs bb: OR=1.338, 95%CI=1.013-1.768; aa+ba vs bb: OR=1.474, 95%CI=1.002-2.170). This meta-analysis indicated that the eNOS T-786C polymorphism is associated with elevated cancer risk; the G894T polymorphism contributes to susceptibility to breast cancer and cancer generally in females; and the 4a/b polymorphism may be associated with prostate cancer risk.