Katkoori Venkat R, Jia Xu, Shanmugam Chandrakumar, Wan Wen, Meleth Sreelatha, Bumpers Harvey, Grizzle William E, Manne Upender
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-7331, USA.
Clin Cancer Res. 2009 Apr 1;15(7):2406-16. doi: 10.1158/1078-0432.CCR-08-1719.
Several studies have examined the prognostic value of the codon 72 polymorphism of the p53 gene in colorectal adenocarcinoma, but none have addressed patient race/ethnicity. Therefore, this study assessed the prognostic value of this polymorphism in African American and Caucasian colorectal adenocarcinoma patients separately.
Colorectal adenocarcinomas from 137 African Americans and 236 non-Hispanic Caucasians were assessed for p53 mutations and genotyped for the codon 72 polymorphism. The phenotypes were correlated with p53 mutational status, clinicopathologic features, and patient survival using the chi(2) test and Kaplan-Meier and Cox regression models.
The incidence of p53 mutations was similar in African American and Caucasian patients (50% versus 54%, respectively); however, the homozygous Pro72 allele frequency was higher in African Americans (17%) as compared with Caucasians (7%). In contrast, the homozygous Arg72 allele frequency was higher in Caucasians (36%) than in African Americans (19%). In African Americans but not Caucasians, the Pro/Pro phenotype significantly correlated with a higher incidence of missense p53 mutations and with nodal metastasis. African Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality (log-rank P = 0.005 versus. P = 0.886) and risk of death due to colorectal adenocarcinoma (hazard ratio, 2.15; 95% confidence interval, 1.02-4.53 versus hazard ratio, 1.60; 95% confidence interval, 0.69-3.18) than those with the phenotype Arg/Arg or Arg/Pro.
The higher frequency of the Pro/Pro phenotype of p53 in African American patients with colorectal adenocarcinoma is associated with an increased incidence of p53 mutations, with advanced tumor stage, and with short survival.
多项研究探讨了p53基因密码子72多态性在结肠直肠癌中的预后价值，但均未涉及患者的种族/民族。因此，本研究分别评估了该多态性在非裔美国人和白人结肠直肠癌患者中的预后价值。
对137名非裔美国人和236名非西班牙裔白人的结肠直肠癌进行p53突变评估，并对密码子72多态性进行基因分型。使用卡方检验、Kaplan-Meier和Cox回归模型将表型与p53突变状态、临床病理特征及患者生存率进行关联分析。
非裔美国人和白人患者中p53突变的发生率相似（分别为50%和54%）；然而，非裔美国人中纯合Pro72等位基因频率（17%）高于白人（7%）。相反，白人中纯合Arg72等位基因频率（36%）高于非裔美国人（19%）。在非裔美国人而非白人中，Pro/Pro表型与错义p53突变的较高发生率及淋巴结转移显著相关。具有Pro/Pro表型的非裔美国人而非白人的死亡率显著更高（对数秩检验P = 0.005，而P = 0.886），且因结肠直肠癌死亡的风险也更高（风险比为2.15；95%置信区间为1.02 - 4.53，而风险比为1.60；95%置信区间为0.69 - 3.18），高于具有Arg/Arg或Arg/Pro表型的患者。
在患有结肠直肠癌的非裔美国患者中，p53的Pro/Pro表型频率较高与p53突变发生率增加、肿瘤晚期及生存期短相关。
