Zhang Zun-Wu, Newcomb Paul, Hollowood Andrew, Feakins Roger, Moorghen Moganaden, Storey Alan, Farthing Michael J G, Alderson Derek, Holly Jeff
Division of Surgery, Bristol Royal Infirmary, University of Bristol, Bristol BS2 8HW, UK.
Clin Cancer Res. 2003 Jun;9(6):2151-6.
A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility and prognosis. To examine the role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients with or without the cancer.
DNA samples were extracted from archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP.
The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were 7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of codon 72 Arg p53 with age was observed in patients with gastric cancer, but not in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a significantly higher frequency of homozygous Arg allele than those with non-cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and gender, a logistic regression analysis suggested that the risk for a p53 Arg homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4-7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous patients. No close relationship was observed among patient gender, tumor histological type, p53 protein expression, and codon 72 genotype distribution.
These findings indicate that codon 72 Arg p53 may be associated with a prolonged survival for patients who have had gastric adenocarcinoma, especially non-cardia adenocarcinoma. It may confer, however, a different role on patients who suffer cardia gastric adenocarcinoma.
肿瘤抑制基因TP53第72位密码子的常见多态性与人类癌症易感性及预后相关。为研究该多态性在胃腺癌中的作用,我们对397例患有或未患癌症的患者进行了检测。
从存档的胃肿瘤组织和/或胃腺癌及非癌症患者的正常组织中提取DNA样本。通过PCR-RFLP确定TP53第72位密码子的基因型。
Pro/Pro、Arg/Pro和Arg/Arg的总体基因型频率分别为7.3%、45.1%和47.6%。在胃癌患者中观察到第72位密码子的Arg p53频率随年龄显著逐步增加,但在非癌症患者中未观察到(P = 0.01)。贲门癌患者的纯合Arg等位基因频率显著高于非贲门肿瘤患者(P = 0.03)或非癌症患者。在对年龄和性别进行调整后,逻辑回归分析表明,p53 Arg纯合患者发生贲门癌的风险是p53 Pro纯合和p53 Arg/Pro杂合患者的3.1倍(95%置信区间,1.4 - 7.3)。未观察到患者性别、肿瘤组织学类型、p53蛋白表达与第72位密码子基因型分布之间的密切关系。
这些发现表明,第72位密码子的Arg p53可能与胃腺癌患者(尤其是非贲门腺癌患者)的生存期延长有关。然而,它可能对患有贲门胃腺癌的患者具有不同的作用。