Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study

Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study
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DOI:
10.1093/jnci/90.9.675
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发表时间:
1998-05-06
期刊:
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子:
--
通讯作者:
Clarke, PA
Clarke, PA
中科院分区:
其他
文献类型:
--
作者:
Andreyev, HJN;Norman, AR;Clarke, PA

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背景:Kirsten ras (Ki-ras)基因突变发生在结直肠腺瘤向癌发展的早期。这项合作研究的目的是通过使用来自世界各地结直肠癌患者的数据来阐明Ki-ras突变、患者预后和肿瘤特征之间的关系。方法:已发表Ki-ras和结直肠癌数据的研究人员被邀请为输入数据库的每位患者完成一份问卷。采用双侧统计检验对数据进行分析。结果:患者(n = 2721)来自13个国家的22组。37.7%的肿瘤检测到Ki-ras密码子12(野生型= GGT =甘氨酸)或密码子13(野生型= GGC =甘氨酸)突变;80.8%(584 / 723)的特异突变发生在密码子12,78.1%(565 / 723)的特异突变发生在任意一个密码子的第二碱基。突变与性别、年龄、肿瘤部位或Dukes分期无关。散发性肿瘤患者的突变率与癌症易感原因患者的突变率相当。低分化肿瘤较少发生突变(P = 0.002),多因素分析表明突变的存在增加了复发的风险(P = 0.002)
Background: Kirsten ras (Ki-ras) gene mutations occur early in the progression of colorectal adenoma to carcinoma. The aim of this collaborative study was to clarify the association between Ki-ras mutations, patient outcome, and tumor characteristics by use of data from colorectal cancer patients worldwide, Methods: Investigators who had published data on Ki-ras and colorectal cancer were invited to complete a questionnaire for each patient entered into a database. Two-sided statistical tests were used to analyze data. Results: Patients (n = 2721) were recruited from 22 groups in 13 countries. Mutations of Ki-ras codon 12 (wild type = GGT = glycine) or codon 13 (wild type = GGC = glycine) were detected in 37.7% of the tumors; 80.8% (584 of 723) of all the specified mutations occurred in codon 12, and 78.1% (565 of 723) of all the specified mutations were at the second base of either codon. Mutations were not associated with sex, age, tumor site, or Dukes' stage. Mutation rates seen in patients with sporadic tumors were comparable to those observed in patients with a predisposing cause for their cancer. Poorly differentiated tumors were less frequently mutated (P = .002), Multivariate analysis suggested that the presence of a mutation increased risk of recurrence (P