OBJECTIVES: SNP309 polymorphism (T-G) at the promoter region of MDM2 has been reported to cause increased binding affinity of transcriptional activator Sp1 followed by increased MDM2 both in mRNA and protein level. This model was proposed in vitro in the small panel of cell lines that indicated an on average 8-fold higher level of MDM2 mRNA in cells bearing the GG genotype. METHODS: The incidence of SNP309 was determined in a cohort of 158 breast, 17 endometrium, 13 cervix and 45 ovarian cancer tissues by PCR-RFLP. The expression of p53 and MDM2 protein levels in the cohort was immunohistochemically investigated and statistically correlated with SNP309 polymorphism using Pearson chi(2) and t test. RESULTS: No significant difference was observed in the G allele incidence in breast cancer specimens compared to 149 noncancer controls. Furthermore, no statistically significant association of the G allele frequencies and p53 and MDM2 protein expression levels was observed. CONCLUSIONS: Our data clearly show neither association between SNP309 and cancer risk, nor the responsibility of G allele for increased MDM2 or decreased of p53 protein levels in human primary breast tumors.

Department of Oncological and Experimental Pathology Masaryk Memorial Cancer Institute Brno Czech Republic

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Polymorphisms in p53 and the p53 pathway: roles in cancer susceptibility and response to treatment