MDM2 Gene Promoter Polymorphism and Risk of Cervical Cancer in Chinese Population

Abstract

Purpose: Mouse double minute 2 (MDM2) is a key negative regulator of the p53 activity. Recently, a polymorphism in the intronic promoter, SNP309, was shown to influence MDM2 expression and p53 activity. We examined whether the SNP309 was related to the risk of developing cervical cancer among Chinese populations. Experimental Design: We genotyped the MDM2 polymorphism SNP309 of peripheral blood DNA from 110 cervical cancer patients and from 160 controls. Genotyping were confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing. The logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95%CI). Results: We observed that compared with the TT genotype, the GG genotype was associated with significant increased susceptibility to cervical cancer (OR =2.69, 95% CI =1.26-5.71, P=0.008). The relative frequency of each allele was 0.623 for G and 0.377 for T in patients with cervical cancer, and 0.50 for G and 0.50 for T in normal controls (P<;0.05). Furthermore, we also found that the MDM2 SNP309 GG genotype was significantly associated with lymph node metastasis but not tumor histological type, tumor grade and size. Conclusions: Our findings show a significant association between functional polymorphism in MDM2 and increased risk of developing cervical cancer in Chinese population. In addition, the SNP309 GG genotype may be a risk factor for lymph node metastasis of cervical cancer.