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Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer

Katie A Ashton1, Anthony Proietto, Geoffrey Otton

  • 1Discipline of Medical Genetics, School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia.

Gynecologic Oncology
|February 6, 2009
PubMed
Abstract

Insights

Genetic variations in TP53 and MDM2 are linked to higher-grade endometrial cancer. This combination of polymorphisms may also indicate a familial cancer grouping, particularly with a history of breast cancer.

Area of Science:

  • Oncology
  • Genetics
  • Cancer Biology

Background:

  • Endometrial cancer grade determinants are not fully understood, but cell cycle control is implicated.
  • TP53 and MDM2 genes are crucial for cell cycle arrest and apoptosis.
  • Polymorphisms in TP53 and MDM2 can lead to TP53 inactivation and MDM2 overexpression, promoting genetic errors.

Purpose of the Study:

  • To investigate the association between specific polymorphisms in the TP53 and MDM2 genes and endometrial cancer risk and grade.
  • To explore the combined effect of these polymorphisms on endometrial cancer development.
  • To examine the relationship between TP53 polymorphisms, family history of breast cancer, and endometrial cancer.

Main Methods:

  • Genotyping of one MDM2 polymorphism (rs2279744, SNP309) and three TP53 polymorphisms (rs1042522, rs17878362, rs1625895) was performed.
  • The study included 191 endometrial cancer cases and 291 controls.
  • Techniques used included PCR-based fragment analysis, RFLP analysis, and real-time PCR.

Main Results:

  • No significant association was found between individual TP53 or MDM2 SNP309 polymorphisms and endometrial cancer risk.
  • A significant association was observed between the combined genotypes of MDM2 SNP309 and the three TP53 polymorphisms and higher endometrial cancer grade (OR 4.15, p=0.0003).
  • Variant TP53 genotypes were significantly related to a higher frequency of family members with breast cancer (OR 2.78, p=0.004).

Conclusions:

  • The combination of MDM2 SNP309 and TP53 polymorphisms appears to be associated with increased endometrial cancer grade.
  • The observed association between TP53 polymorphisms, endometrial cancer, and a family history of breast cancer suggests a potential low-risk familial cancer grouping.

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