Dataset Information

MDM2 SNP309 is associated with endometrial cancer risk.

ABSTRACT: Mouse double-minute 2 homologue (MDM2) is a key negative regulator of p53, a tumor suppressor gene that initiates cell cycle arrest and apoptosis in response to DNA damage and other cellular stresses. A T > G polymorphism found in the promoter region of MDM2 (SNP309) increases MDM2 expression and thereby attenuates p53 activity. We genotyped the MDM2 polymorphism SNP309 in endometrial cancer case-control studies nested within the Nurses' Health Study (454 cases and 1,132 controls) and the Women's Health Study (137 cases and 411 controls). Due to a significant difference in genotype distribution by ethnicity, we restricted our analyses to Caucasians. We calculated odds ratios and 95% confidence intervals using conditional and unconditional logistic regression adjusted for age at menarche, parity and age at first birth, postmenopausal hormone use at diagnosis, age at menopause and menopausal status at diagnosis, first-degree family history of colon cancer, body mass index at diagnosis, and cigarette smoking status at diagnosis. Women with a heterozygous genotype had no greater risk whereas those with a homozygous variant genotype had a greater risk than women with a wild-type genotype for the MDM2 SNP309 (covariate-adjusted odds ratio, 1.87; 95% confidence interval, 1.29-2.73) for endometrial cancer. We observed no association between age at diagnosis and genotype. Women carrying two copies of the MDM2 SNP309 variant may be at greater risk of endometrial cancer.

SUBMITTER: Terry K

PROVIDER: S-EPMC2728574 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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MDM2 SNP309 is associated with endometrial cancer risk.

Terry Kathryn K McGrath Monica M Lee I-Min IM Buring Julie J De Vivo Immaculata I

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20080401 4

Mouse double-minute 2 homologue (MDM2) is a key negative regulator of p53, a tumor suppressor gene that initiates cell cycle arrest and apoptosis in response to DNA damage and other cellular stresses. A T > G polymorphism found in the promoter region of MDM2 (SNP309) increases MDM2 expression and thereby attenuates p53 activity. We genotyped the MDM2 polymorphism SNP309 in endometrial cancer case-control studies nested within the Nurses' Health Study (454 cases and 1,132 controls) and the Women' ...[more]

PMID: 18398041

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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:BackgroundEvidence suggests that MDM2 T309G polymorphism may be a risk factor for several cancers. Increasing investigations have been conducted on the association of MDM2 T309G polymorphisms with lung cancer risk and have yielded conflicting results. Previous meta-analyses on this issue have reported inconclusive data. The aim of the present study was to derive a more precise estimation of the relationship.Methods and findingsUpdated meta-analyses examining the association between MDM2 T309G polymorphism and lung cancer risk were performed. Separate analyses on ethnicity, smoking status, histological types and gender as well as source of controls were also implemented. Eligible studies were identified for the period up to Feb 2012. Lastly, ten publications including eleven case-control studies were selected for analysis. The overall data failed to indicate a significant association between MDM2 T309G polymorphism and lung cancer risk (GG vs TT OR = 1.14; 95%CI = 0.95-1.37; dominant model: OR = 1.05; 95%CI = 0.92-1.19; recessive model: OR = 1.12; 95%CI = 0.99-1.27). In a subgroup analysis by smoking status, increased lung cancer risk was shown among never-smokers (GG vs TT: OR = 1.76; 95%CI = 1.36-2.29; dominant model: OR = 1.48; 95%CI = 1.22-1.81; recessive model: OR = 1.37; 95%CI = 1.11-1.69). In subgroup analysis by gender, elevated risk was presented among women under a recessive model (OR = 1.29; 95%CI = 1.04-1.59). In the subgroup analysis by ethnicity, histological types and source of controls, no marked associations were observed.ConclusionsCompared to the previous meta-analyses, the results of this study confirmed that MDM2 T309G polymorphism might be a risk factor for lung cancer among never-smokers. However, the data failed to suggest a marked association between the G allele of MDM2 T309G and lung cancer risk among Asians. More interestingly, subgroup analysis by gender indicated that homozygous GG alleles might raise lung cancer risk among females.

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MDM2 SNP309 is associated with endometrial cancer risk.

Publications

MDM2 SNP309 is associated with endometrial cancer risk.

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