Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status

✍ Scribed by Ye Xu; Lihua Yao; Ailian Zhao; Tao Ouyang; Jinfeng Li; Tianfeng Wang; Zhaoqing Fan; Tie Fan; Benyao Lin; Youyong Lu; Yuntao Xie

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 116 KB
• Volume: 122
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23454

✦ Synopsis

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.