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. 2007;9(3):R34.
doi: 10.1186/bcr1682.

Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients

Tatsuya Toyama  1 , Zhenhuan Zhang, Mariko Nishio, Maho Hamaguchi, Naoto Kondo, Hirotaka Iwase, Hiroji Iwata, Satoru Takahashi, Hiroko Yamashita, Yoshitaka Fujii
Affiliations

Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients

Tatsuya Toyama et al. Breast Cancer Res. 2007.

Abstract

Introduction: Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53 (also known as p53) gene (rs1042522) and in the promoter region of the MDM2 gene (SNP309; rs2279744) have been suggested to play roles in many cancers. We investigated whether these SNPs were associated with patient outcome and the effect of adjuvant systemic therapy.

Methods: The genotypes of TP53 codon 72 and MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients (median follow-up, 61.7 months). The effects of several variables on survival were tested by Cox's proportional hazards regression analysis.

Results: We showed that the Pro/Pro genotype of TP53 codon 72 was associated with poorer disease-free survival (DFS) than other genotypes by Kaplan-Meier analysis (P = 0.049) and multivariate Cox's proportional hazards regression analysis (P = 0.047, risk ratio of recurrence = 1.67), whereas MDM2 SNP309 status was not associated with DFS. The association of the Pro/Pro TP53 genotype with poorer DFS was especially significant in patients who received adjuvant chemotherapy (P = 0.009). In contrast, among the patients who had received adjuvant hormonal therapy or no adjuvant systemic therapy, TP53 codon 72 genotype was not associated with DFS.

Conclusion: The Pro/Pro genotype of TP53 codon 72 appears to be an independent prognostic marker in breast cancer patients.

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Figures

Figure 1
Figure 1
Kaplan-Meier survival curves of breast cancer patients. Disease-free survival (DFS) among patients categorized by (a) MDM2 SNP309 status and (b) TP53 codon 72 status. DFS in patients (c) without axillary lymph node involvement and (d) with lymph node metastasis according to their TP53 codon 72 status. NS, not significant.
Figure 2
Figure 2
The effect of adjuvant systemic therapy on prognostic impact of polymorphisms. (a) TP53 codon 72 and adjuvant chemotherapy alone (n = 137); (b) TP53 codon 72 and adjuvant chemotherapy with or without hormonal therapy (n = 281); (c) TP53 codon 72 and adjuvant hormonal therapy alone (n = 195); (d) TP53 codon 72 and no adjuvant systemic therapy (n = 77); (e) MDM2 SNP309 and adjuvant tamoxifen with or without luteinizing hormone-releasing hormone analog (n = 185). DFS, disease-free survival.
See this image and copyright information in PMC

References

    1. Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–310. doi: 10.1038/35042675. - DOI - PubMed
    1. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88:323–331. doi: 10.1016/S0092-8674(00)81871-1. - DOI - PubMed
    1. Michael D, Oren M. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003;13:49–58. doi: 10.1016/S1044-579X(02)00099-8. - DOI - PubMed
    1. Lundgren K, Montes de Oca Luna R, McNeill YB, Emerick EP, Spencer B, Barfield CR, Lozano G, Rosenberg MP, Finlay CA. Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53. Genes Dev. 1997;11:714–725. doi: 10.1101/gad.11.6.714. - DOI - PubMed
    1. Cordon-Cardo C, Latres E, Drobnjak M, Oliva MR, Pollack D, Woodruff JM, Marechal V, Chen J, Brennan MF, Levine AJ. Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res. 1994;54:794–799. - PubMed

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