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韩国幽门螺杆菌相关性胃癌中 p53 密码子 72 基因多态性与 p53 蛋白表达的差异。

The discrepancy between genetic polymorphism of p53 codon 72 and the expression of p53 protein in Helicobacter pylori-associated gastric cancer in Korea.

机构信息

Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam, Gyeonggi-do 463-707, South Korea.

出版信息

Dig Dis Sci. 2010 Jan;55(1):101-10. doi: 10.1007/s10620-008-0688-x. Epub 2009 Jan 29.

Abstract

The p53 gene has been referred to as 'the guardian of the genome' because it controls apoptosis and cell cycle arrest. The purpose of this study was to evaluate the association of p53 codon 72 genetic polymorphism and the p53 immunohistochemistry with Helicobacter pylori-associated gastroduodenal diseases, including gastric cancer. This study included 1,852 subjects: controls and patients with gastric cancer, dysplasia, benign gastric ulcers, and duodenal ulcers (DU). Biallelic polymorphism was genotyped by restriction fragment length polymorphism. Immunohistochemical analysis for the detection of mutant type p53 expression was performed. The frequency of the Pro/Pro allele of the p53 codon 72 was higher in the patients with H. pylori-positive dysplasia than in controls (OR: 2.3, 95% CI: 1.3-4.3), but it was less frequent among patients with a H. pylori-positive DU (OR: 0.5, 95% CI: 0.3-0.8). However, there was no significant association with gastric cancer, including the location, stage, or histological type of gastric cancer. Expression of a mutant type of p53 protein was detected in 6.3% of dysplastic tissues and 26.5% of cancerous tissues compared 0% in the controls. Positive expression was higher in the intestinal type of cancer (34.9%) than in the diffuse type (15.0%; P = 0.001). These results suggest that genetic polymorphism of p53 codon 72 played a role in the determination of H. pylori-associated gastroduodenal diseases, but p53 immunostaining did not correlate with those of the p53 genetic polymorphism analysis.

摘要

p53 基因被称为“基因组的守护者”,因为它控制着细胞凋亡和细胞周期停滞。本研究旨在评估 p53 密码子 72 遗传多态性与 p53 免疫组化与幽门螺杆菌相关胃十二指肠疾病(包括胃癌)的关联。本研究纳入了 1852 名受试者:对照组和胃癌、异型增生、良性胃溃疡和十二指肠溃疡(DU)患者。通过限制性片段长度多态性分析双等位基因多态性。进行 p53 突变型表达的免疫组化分析。p53 密码子 72 的 Pro/Pro 等位基因在 H. pylori 阳性异型增生患者中的频率高于对照组(OR:2.3,95%CI:1.3-4.3),但在 H. pylori 阳性 DU 患者中较少见(OR:0.5,95%CI:0.3-0.8)。然而,与胃癌(包括胃癌的位置、分期或组织学类型)之间没有显著相关性。与对照组相比,异型增生组织中检测到突变型 p53 蛋白的表达率为 6.3%,癌组织中为 26.5%。在肠型癌(34.9%)中阳性表达率高于弥漫型癌(15.0%;P = 0.001)。这些结果表明,p53 密码子 72 的遗传多态性在决定 H. pylori 相关胃十二指肠疾病中起作用,但 p53 免疫组化与 p53 遗传多态性分析结果无关。

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