Polymorphisms of p53 codon 72 and MDM2 promoter 309 and the risk of endometrial cancer

Abstract

Genetic polymorphisms of p53 and its negative regulator murine double minute 2 homolog (MDM2) have been shown to be closely associated with tumorigenesis in a variety of human cancers. In the present study, single nucleotide polymorphism (SNP) at p53 codon 72 and MDM2 promoter 309 was examined for germline DNA samples from 102 endometrial cancer cases and 95 controls using polymerase chain reaction-based fragment analysis. There were no significant differences in the genotype and allele prevalence between control subjects and endometrial cancer patients for p53 codon 72. The GG genotype frequency of MDM2-SNP309 was statistically higher in endometrial cancer patients than that in normal healthy women when compared with the TG genotype (P= 0.0088). However, no statistically significant differences were found between the TT and TG or GG genotype frequencies and allele prevalence. Interestingly, the combination of the homozygous Arg/Arg genotype of p53 codon 72 and homozygous GG genotype of MDM2 SNP309 polymorphisms was significantly associated with the risk of endometrial cancer (odds ratio = 3.28, 95% confidence interval = 1.13 to 9.53, P= 0.0212). The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population.

Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk

“…Roh et al (2004) demonstrated that there is a significant association between p53 gene polymorphisms and EC risk in Korean women. Nunobiki et al (2009) also confirmed that the Pro/Pro genotype of p53 codon 72 polymorphism may increase the risk of EC in the Japanese population. Ashton et al (2009) showed that p53 gene polymorphisms appear to be related to a higher grade of EC.…”

“…According to the inclusion criteria, only 10 case-control studies (Esteller et al, 1997;Peller et al, 1999;Agorastos et al, 2004;Roh et al, 2004;Niwa et al, 2005;Ueda et al, 2006;Ashton et al, 2009;Nunobiki et al, 2009;Zubor et al, 2009;Ghasemi et al, 2010) with full-text were included in this meta-analysis and 21 studies were excluded. The flow chart for the study selection is summarized in Figure 1.…”

Association between MDM2 SNP309 polymorphism and endometrial cancer risk in Polish women

“…The homozygous variants of wild p53 codon 72 and mutant MDM2 promoter 309 may cooperatively increase the risk of endometrial cancer in a Japanese population [28]. The homozygous GG genotype of SNP309 polymorphism was also associated with the postmenopausal status and type I endometrial cancer in Japanese women [29].…”

“…MDM2 gene SNP309 polymorphisms have been studied as a risk factor for endometrial cancer [15,19,[27][28][29]. Terry et al showed that women carrying GG genotype of MDM2 SNP309 polymorphism may be at greater risk of endometrial cancer [15].…”

Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

“…Roh et al have demonstrated that there is a significant association between p53 gene polymorphisms and cervical cancer risk in Korean women (Roh et al, 2004). Other genetic studies also confirmed that the Pro/Pro genotype of p53 codon 72 polymorphism may increase the risk of cervical cancer in Japanese populations and p53 gene polymorphisms appear to be related to a higher grade of cervical cancer (Ashton et al, 2009;Nunobiki et al, 2009). However, Zubor et al did not demonstrate any significant association between p53 codon 72 polymorphism and the risk of cervical cancer in Caucasians (Zubor et al, 2009).…”