title: Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene status.
abstract: In vitro studies suggest that p53 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 p53 gene status. In our study, we examined the p53 codon 72 genotype and p53 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 p53 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 p53 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 p53 tumor (HR = 2.5; 95%CI = 1.4-4.4; p = 0.003). We conclude that the effect of p53 codon 72 genotype on breast cancer survival is dependent on p53 gene status, the P/P variant is strongly associated with poor prognosis among patients with a wild-type p53 tumor.
authors.affiliation: Breast Center, Beijing Cancer Hospital and Institute, Peking University School of Oncology, 100036 Beijing, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Lihua
authors.initials: L
authors.lastname: Yao
authors.forename: Ailian
authors.initials: A
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fan
authors.forename: Tie
authors.initials: T
authors.lastname: Fan
authors.forename: Benyao
authors.initials: B
authors.lastname: Lin
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D003062:Codon; D017931:DNA Primers; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D017741:Survivors
chemical_list: D003062:Codon; D017931:DNA Primers