TP53-binding protein variants and breast cancer risk: a case-control study

Breast Cancer Res. 2005;7(4):R502-5. doi: 10.1186/bcr1038. Epub 2005 May 6.

Abstract

Introduction: The TP53-binding protein (53BP1) has been shown to influence TP53-mediated transcriptional activation, thus playing a pivotal role in DNA damage signalling. Genetic aberrations in TP53 and in ATM and CHEK2 predispose to cancer. We have therefore examined the effects of 53BP1 single nucleotide polymorphisms (D353E, G412S, and K1136Q) and the novel 53BP1 6bp deletion (1347_1352delTATCCC) on breast cancer risk.

Methods: Allelic discrimination was performed to investigate the frequencies of 53BP1 D353E, G412S, and K1136Q and of 1347_1352delTATCCC in 353 patients with breast cancer and 960 control individuals.

Results: No significant association of 53BP1 D353E, G412S, or K1136Q with breast cancer risk was detected. 53BP1 1347_1352delTATCCC, leading to the loss of an isoleucine and a proline residue, showed a nonsignificant inverse association with breast cancer risk (odds ratio = 0.61, 95% confidence interval = 0.22 to 1.68, P = 0.34).

Conclusion: The lack of association casts doubt on the putative effects of D353E, G412S, and K1136Q on breast cancer risk. Investigating a larger study cohort might elucidate the influence of the 6bp deletion 1347_1352delTATCCC. Studying the functional effect and the impact of this variant on the risk of other cancers may be revealing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Middle Aged
  • Odds Ratio
  • Phosphoproteins / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Tumor Suppressor p53-Binding Protein 1

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1