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Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status
Author(s) -
Xu Ye,
Yao Lihua,
Zhao Ailian,
Ouyang Tao,
Li Jinfeng,
Wang Tianfeng,
Fan Zhaoqing,
Fan Tie,
Lin Benyao,
Lu Youyong,
Xie Yuntao
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23454
Subject(s) - genotype , breast cancer , exon , biology , gene , wild type , medicine , cancer , microbiology and biotechnology , oncology , gastroenterology , genetics , mutant
Abstract In vitro studies suggest that p 53 codon 72 genotype alters the apoptotic capacity of p53 protein, with the 72 arginine (R) form of wild‐type p53 harboring a greater apoptosis‐inducing potential than the 72 proline (P) variant. The aim of this study was to investigate whether the association between the p53 codon 72 genotype and breast cancer survival was modified by p 53 gene status. In our study, we examined the p 53 codon 72 genotype and p 53 mutations (through exons 4–9) in paraffin‐embedded specimens from 414 breast cancer patients with a median follow‐up of 8.2 years. We report that the p 53 codon 72 genotype was significantly associated with disease‐free survival (DFS, p = 0.02) but not with disease‐specific survival (DSS, p = 0.24) in the entire study population ( n = 414). In contrast, the codon 72 genotype was strongly associated with both DFS ( p = 0.001) and DSS ( p = 0.04) among patients with a wild‐type p 53 tumor ( n = 346), patients with the P/P variant had worse DFS and DSS than did those with the P/R or R/R variant in this subgroup of patients. More importantly, as compared with the P/R or R/R variant, the P/P variant remained an independent prognostic factor of DFS among patients with a wild‐type p 53 tumor (HR = 2.5; 95%CI = 1.4–4.4; p = 0.003). We conclude that the effect of p 53 codon 72 genotype on breast cancer survival is dependent on p 53 gene status, the P/P variant is strongly associated with poor prognosis among patients with a wild‐type p 53 tumor. © 2008 Wiley‐Liss, Inc.