Impact of MDM2 polymorphism: increased risk of developing colorectal cancer and a poor prognosis in the Tunisian population

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Abstract

Introduction

MDM2 was originally identified as an oncoprotein that binds to p53 and inhibits p53-mediated transactivation. Scientists have described functional single-nucleotide polymorphisms (SNP) in the MDM2 gene. They showed that the genotype of SNP 309 induces an increase in the level of MDM2 protein, which causes attenuation of the p53 pathway. In this study, we sought to investigate whether this polymorphism was related to risk of colorectal cancer and whether there were relationships between SNP 309 and protein expression or clinicopathological variables in Tunisian patients.

Materials and methods

To investigate the effect of this polymorphism in colorectal cancer pathogenesis, we genotyped 167 patients and 167 blood donors. Immunohistochemistry was performed on normal mucosa and tumor.

Results

The rates of MDM2 genotypes were 6.6% for wild-type (T/T) and 93.4% for the SNP 309 polymorphic genotype (T/G and G/G) in patients and 38.3 and 61.7% in controls, respectively. There were significant differences in the frequencies of genotypes between patients and controls (P<0.01). We did not find any relationship between genotypes and clinicopathological features of patients, except in the case of the nonmucinous histological subtype (P=0.001). Moreover, we found that patients with the wild-type genotype (T/T) had significantly more favorable clinical outcome than did patients with the SNP 309 genotype (T/G, G/G) (P=0.005). In addition, we found an association between positive expression of p53 and polymorphic genotypes of MDM2 (T/G, G/G) (P=0.037). There was a significant association between tumoral immunostaning and MDM2 polymorphism (P=0.01).

Conclusion

Our results suggest that the MDM2 polymorphism is significantly associated with colorectal cancer risk and may provide useful prognostic information for Tunisian patients with colorectal cancer.

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