p53 and p21 genetic polymorphisms and susceptibility to endometrial cancer

Recently, there has been considerable interest in the association of specific cancers with single nucleotide polymorphisms (SNPs). In this regard, genetic polymorphism at codon 72 (CCC/proline to CGC/arginine [Pro(72)Arg]) of the p53 gene is one of the most frequently studied subjects. An association between endometrial cancer and the polymorphism at codon 31 (AGC/serine to AGA/arginine [Ser(31)Arg]) of the p21 gene, which is known to be a downstream mediator of p53, has also been reported.

The authors designed a hospital-based case-control study of 95 endometrial cancer patients and 285 non-cancer controls. For the determination of p53 and p21 polymorphism, allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism assay was applied, respectively.

We found statistically significant differences in the frequency of the p53 and p21 genotypes between these two groups (P < 0.001), respectively. The p53 genotypes containing the Pro allele were significantly associated with endometrial cancer with an odds ratio (OR) of 3.56 (95% confidence interval [CI] 2.10-6.04). Also, homozygous carriers of the p21 Ser allele showed a substantially increased risk of developing endometrial cancer (OR 2.68, 95% CI 1.59-4.51) as compared to homozygous and heterozygous carriers of the Arg allele. In addition, the combination of the pro allele containing genotypes of p53 and the Ser homozygous genotype of p21 posed a remarkably increased risk (OR 9.55, 95% CI 4.30-21.24) of endometrial cancer development. These significant differences were maintained throughout the groups after they were stratified by menopausal status.

These data suggest that there is a significant association between the genetic polymorphisms of p53, p21, and specific combinations of the at-risk genotypes of these genes and the risk of developing endometrial cancer in Korean women.