Biological Significance of Allele-Specific Loss of the P53 Gene in Breast Carcinomas

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Research published in the journal Breast Cancer Research and Treatment has shed light on the role of the p53 tumor suppressor gene in breast cancer. The study, conducted by P.P. Wegman and colleagues at the University of Orebro, investigated the biological relevance of the p53 gene's polymorphic variant, Arg/Pro, in codon 72 heterozygous breast cancer patients. The researchers analyzed 199 postmenopausal cases for loss of heterozygosity (LOH) using MegaBACE and found that LOH was present in 62.3% of patients, with the Pro allele being significantly more often deleted compared to the Arg allele.

Key Takeaways:

  • The p53 tumor suppressor gene plays a central role in defending against cancer, including breast cancer, and contains a polymorphic variant (Arg/Pro) at codon 72 that has different biological properties regarding apoptosis and cell cycle arrest.
  • 199 postmenopausal breast cancer cases were analyzed for LOH, with 124 (62.3%) patients showing LOH at the codon 72 site.
  • The Pro allele was significantly more often deleted compared to the Arg allele, with a P-value of 0.001.
  • Patients with LOH of the Arg allele were diagnosed at an earlier age (mean age 62.5 years) compared to those with loss of the Pro allele (mean age 69.2 years), with a P-value of 0.011.
  • LOH of the Arg allele was associated with worse survival, with a P-value of 0.05.
  • LOH in comparison to ROH correlated significantly with increased S-phase fraction.
  • Tumor size, stage, or number of positive lymph nodes was not related to LOH.

Statistics:

  • 199 postmenopausal breast cancer cases were analyzed for LOH.
  • 62.3% of patients (124 out of 199) showed LOH at the codon 72 site.
  • The Pro allele was deleted in 103 patients, while the Arg allele was deleted in 21 patients.
  • Patients with LOH of the Arg allele were diagnosed at an average age of 62.5 years.
  • Patients with loss of the Pro allele were diagnosed at an average age of 69.2 years.
  • Patients with LOH of the Arg allele showed a worse survival rate, with a 0.05 P-value.

Sources:

  • Wegman, P. P., et al. (2009). "Biological significance of allele specific loss of the p53 gene in breast carcinomas." Breast Cancer Research and Treatment, 118(1), 15-20.
  • University of Orebro, Dept. of Health & Med Science, S-70182 Orebro, Sweden.
  • Springer, 233 Spring St., New York, NY 10013, USA.