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Open Access

Prognostic value genotypes and LOH at TP53 codon 72 and TP53mutations in primary breast cancer

  • M Kyndi1, 2,
  • J Alsner1,
  • LL Hansen3,
  • FB Sørensen2 and
  • J Overgaard1
Breast Cancer Research20057(Suppl 2):P4.49

https://doi.org/10.1186/bcr1179

Published: 17 June 2005

Keywords

Breast CancerDistant MetastasisBreast CarcinomaPrimary Breast CancerTP53 Mutation

Background

Recent data suggest that the Arg72Pro polymorphism of the TP53 gene is correlated to TP53 mutations and prognosis in breast cancer [1, 2]. In addition, LOH with retention of the Arg allele has been associated with reduced disease-free survival and overall survival [3].

Patients and methods

In the period January 1990–1994 a consecutive cohort of 204 Danish women were diagnosed with primary breast cancer. TP53 mutations were assessed by denaturing gradient gel electrophoresis analysis and DNA sequencing. The Arg72Pro polymorphism was measured in DNA extracted from blood lymphocytes and LOH was measured in DNA extracted from invasive breast carcinomas by a method including PCR, primer extension reactions and denaturing high-performance liquid chromatography analyses [4].

Results

Mutations in the TP53 gene in tumour DNA were associated with a significantly higher probability of distant metastases (P < 0.0001). The Arg72Pro polymorphism was neither significantly associated with TP53 mutations (P > 0.2) nor with probability of distant metastases (P > 0.2). Among patients heterozygous at TP53 codon 72, LOH in tumour tissue was significantly associated with TP53 mutations – with 10 out of 40 patients with LOH carrying a TP53 mutation but only one out of 28 patients with no LOH (P = 0.04). However, patients with LOH at TP53 codon 72 did not have a significantly higher probability of distant metastases as compared with patients with no LOH (P > 0.2). But within the group of patients with LOH, a significantly higher probability of distant metastases was found for patients with retention of the Pro allele (11/24) as compared with patients with retention of the Arg allele (2/16) (P = 0.04). Among patients with retention of Pro, five patients out of 24 patients (21%) had TP53 mutations as compared with five patients out of 16 patients (31%) with retention of Arg.

Conclusion

Our findings suggest that the Arg72Pro polymorphism is neither associated with TP53 mutations nor with breast cancer prognosis. However, LOH at codon 72 among heterozygous patients might be associated with TP53 mutations, and patients with retention of the Pro allele might experience a poorer prognosis as compared with patients with retention of the Arg allele.

Authors’ Affiliations

(1)
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark
(2)
Department of Pathology, Aarhus University Hospital, Denmark
(3)
Department of Human Genetics, University of Aarhus, Denmark

References

  1. Langerod A, Bukholm IR, Bregard A, Lonning PE, Andersen TI, Rognum TO, et al: The TP53 codon 72 polymorphism may affect the function of TP53 mutations in breast carcinomas but not in colorectal carcinomas. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1684-1688.PubMedGoogle Scholar
  2. Goode EL, Dunning AM, Kuschel B, Healey CS, Day NE, Ponder BA, et al: Effect of germ-line genetic variation on breast cancer survival in a population-based study. Cancer Res. 2002, 62: 3052-3057.PubMedGoogle Scholar
  3. Bonafe M, Ceccarelli C, Farabegoli F, Santini D, Taffurelli M, Barbi C, et al: Retention of the p53 codon 72 arginine allele is associated with a reduction of disease-free and overall survival in arginine/proline heterozygous breast cancer patients. Clin Cancer Res. 2003, 9: 4860-4864.PubMedGoogle Scholar
  4. Wu G, Hua L, Zhu J, Mo QH, Xu XM: Rapid, accurate genotyping of beta-thalassaemia mutations using a novel multiplex primer extension/denaturing high-performance liquid chromatography assay. Br J Haematol. 2003, 122: 311-316. 10.1046/j.1365-2141.2003.04431.x.View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central 2005

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