Impact of MDM2, TP53 and P14ARF Polymorphisms on Endometrial Cancer Risk and Onset

In Vivo. 2019 May-Jun;33(3):917-924. doi: 10.21873/invivo.11559.

Abstract

Background/aim: The aim of this study was to determine the joint effect of single nucleotide polymorphisms (SNPs) of MDM2, TP53, and CDKN2A (P14ARF) genes on the onset and course of endometrial cancer (EC) in postmenopausal women.

Materials and methods: The study group consisted of 144 EC women and 50 non-cancer controls. MDM2 rs22279744, TP53 rs1042522, and P14ARF rs3088440, rs3731217, and rs3731245 SNPs were analysed.

Results: The double-SNP combinations T-C, T-T, or T-G in MDM2 SNP 309 and P14ARF polymorphisms decreased EC risk. The triple-SNP combinations T-C-T, T-C-G, or T-T-G in MDM2 SNP and two P14ARF polymorphisms decreased EC risk. The multiple-SNP combination T-C-T-G in MDM2 and three P14ARF polymorphisms decreased EC risk. The G-Arg-C-T-G carriers were at increased EC risk, while the T-Arg-C-T-G carriers were at decreased EC risk.

Conclusion: MDM2 SNP309 plays a role in EC onset in postmenopausal women.

Keywords: CDKN2A; MDM2; P14ARF; TP53; endometrial cancer; genetic susceptibility; single nucleotide polymorphisms (SNPs).

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Endometrial Neoplasms / epidemiology*
  • Endometrial Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Postmenopause
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Risk
  • Tumor Suppressor Protein p14ARF / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2