14 research outputs found

    MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk

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    The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744) facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649), located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333) located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954) and patients suffering from ovarian (n = 1,927), breast (n = 1,271), endometrial (n = 895) or prostatic cancer (n = 641), we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively). In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk

    MDM2 Promoter SNP344T>A (rs1196333) Status Does Not Affect Cancer Risk

    Get PDF
    The MDM2 proto-oncogene plays a key role in central cellular processes like growth control and apoptosis, and the gene locus is frequently amplified in sarcomas. Two polymorphisms located in the MDM2 promoter P2 have been shown to affect cancer risk. One of these polymorphisms (SNP309T>G; rs2279744) facilitates Sp1 transcription factor binding to the promoter and is associated with increased cancer risk. In contrast, SNP285G>C (rs117039649), located 24 bp upstream of rs2279744, and in complete linkage disequilibrium with the SNP309G allele, reduces Sp1 recruitment and lowers cancer risk. Thus, fine tuning of MDM2 expression has proven to be of significant importance with respect to tumorigenesis. We assessed the potential functional effects of a third MDM2 promoter P2 polymorphism (SNP344T>A; rs1196333) located on the SNP309T allele. While in silico analyses indicated SNP344A to modulate TFAP2A, SPIB and AP1 transcription factor binding, we found no effect of SNP344 status on MDM2 expression levels. Assessing the frequency of SNP344A in healthy Caucasians (n = 2,954) and patients suffering from ovarian (n = 1,927), breast (n = 1,271), endometrial (n = 895) or prostatic cancer (n = 641), we detected no significant difference in the distribution of this polymorphism between any of these cancer forms and healthy controls (6.1% in healthy controls, and 4.9%, 5.0%, 5.4% and 7.2% in the cancer groups, respectively). In conclusion, our findings provide no evidence indicating that SNP344A may affect MDM2 transcription or cancer risk

    Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer

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    BACKGROUND: While large GWAS analyses have not found convincing associations between MDM2 promoter SNP55 and gynaecological cancers, SNP55 is in linkage disequilibrium with two other functional SNPs in the same promoter, likely to obscure associations between single SNPs and cancer risk. Here, we assessed the impact of SNP55 on risk of endometrial and ovarian cancer, including sub-analyses stratified for other functional SNPs in the region. MATERIAL AND METHODS: Using a custom LightSNiP assay, we genotyped SNP55 in two large hospital-based cohorts of patients with ovarian (n = 1,332) and endometrial (n = 1,363) cancer and compared genotypes to healthy female controls (n = 1,858). RESULTS: Among individuals harbouring the SNP309TT genotype, the minor SNP55T-allele was associated with a reduced risk of endometrial (dominant model: OR = 0.63; CI = 0.45-0.88; p = 0.01). Regardless of the genotype in neighbouring SNPs, the SNP55T-allele was also associated with a reduced risk of endometrial cancer before 50 years of age (dominant model: OR = 0.56; CI = 0.34-0.90; p = 0.02). No association between SNP55 status and ovarian cancer risk was observed. CONCLUSIONS: MDM2 SNP55T-allele may correlate with reduced risk for endometrial cancer in a SNP309T-, but not SNP309G, context
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