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泌尿系统癌症中p53基因密码子72多态性的等位基因频率

Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers.

作者信息

Wu W J, Kakehi Y, Habuchi T, Kinoshita H, Ogawa O, Terachi T, Huang C H, Chiang C P, Yoshida O

机构信息

Department of Urology, Faculty of Medicine, Kyoto University, Japan.

出版信息

Jpn J Cancer Res. 1995 Aug;86(8):730-6. doi: 10.1111/j.1349-7006.1995.tb02461.x.

Abstract

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.

摘要

p53肿瘤抑制基因的改变在许多人类肿瘤的发生发展中似乎起着重要作用。野生型p53基因在密码子72处存在多态性,表现为精氨酸(CGC)或脯氨酸(CCC)基因型,最近有报道称其与吸烟相关肺癌的遗传易感性有关。为了确定这种p53基因型是否会影响个体患泌尿系统癌症的风险和/或其进展,我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法,检测了85例肾细胞癌患者、151例尿路上皮癌患者、33例睾丸癌患者、28例前列腺癌患者以及56例无肿瘤疾病患者中该多态性的等位基因频率。肾细胞癌患者(29.4%、55.3%、15.3%)、尿路上皮癌患者(45.7%、39.7%、14.6%)、睾丸癌患者(45.4%、48.5%、6.1%)或前列腺癌患者(42.9%、50.0%、7.1%)中三种基因型(精氨酸/精氨酸、精氨酸/脯氨酸、脯氨酸/脯氨酸)的等位基因分布与正常对照组相比无显著差异。然而,肾细胞癌和尿路上皮癌(与吸烟相关的癌症)中的脯氨酸/脯氨酸基因型比前列腺癌和睾丸癌(与吸烟无关的癌症)中的更为常见,具有临界显著性(P = 0.0881)。三种基因型的频率与每种肿瘤的分级或分期之间没有特定的相关性。泌尿系统癌症的遗传易感性与p53基因密码子72多态性的关联不像之前对日本肺癌患者的研究那么明确,但这种多态性可能在尿路上皮癌和肾细胞癌中起一定作用,在这些癌症中吸烟是一个流行病学危险因素。

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