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


CONCLUSIONS
The Pro/Pro genotype of TP53 codon 72 appears to be an independent prognostic marker in breast cancer patients.
Toyama
Tatsuya
T
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. toyamat-ncu@umin.ac.jp
Zhang
Zhenhuan
Z
Nishio
Mariko
M
Hamaguchi
Maho
M
Kondo
Naoto
N
Iwase
Hirotaka
H
Iwata
Hiroji
H
Takahashi
Satoru
S
Yamashita
Hiroko
H
Fujii
Yoshitaka
Y
D001483:Base Sequence; D001943:Breast Neoplasms / Q000628:therapy*; D003062:Codon; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011392:Proline; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis; D016896:Treatment Outcome
D003062:Codon; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D011392:Proline; D051736:Proto-Oncogene Proteins c-mdm2