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MDM2SNP309 does not associate with elevated MDM2 protein expression or breast cancer risk
Daniel Krekac1, Kristyna Brozkova, Dana Knoflickova
1Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Oncology
|June 13, 2008
Summary
The MDM2 SNP309 polymorphism (T-G) does not appear to increase cancer risk or affect MDM2/p53 protein levels in human breast tumors, contrary to in vitro findings.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The MDM2 gene promoter contains SNP309 (T-G), a polymorphism potentially influencing MDM2 expression.
- In vitro studies suggested the GG genotype increases Sp1 binding, leading to higher MDM2 mRNA and protein levels.
Purpose of the Study:
- To investigate the association of MDM2 SNP309 polymorphism with cancer risk.
- To determine if SNP309 influences p53 and MDM2 protein expression in primary human tumors.
Main Methods:
- Genotyping of SNP309 using PCR-RFLP in cancer tissues (breast, endometrium, cervix, ovarian) and controls.
- Immunohistochemical analysis of p53 and MDM2 protein expression.
- Statistical correlation of SNP309 allele frequencies with protein levels and cancer incidence.
Main Results:
- No significant difference in G allele incidence was found between breast cancer patients and non-cancer controls.
- No statistically significant association was observed between G allele frequencies and p53 or MDM2 protein expression levels.
Conclusions:
- The MDM2 SNP309 polymorphism is not associated with cancer risk in the studied human cohorts.
- The G allele of SNP309 does not appear to be responsible for increased MDM2 or decreased p53 protein levels in primary breast tumors.
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