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

H.J.N. Andreyev, A.R. Norman, D. Cunningham, J.R. Oates, P.A. Clarke, Nadia Urosevic

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669 Citations (Scopus)


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
Original languageEnglish
Pages (from-to)675-684
JournalJournal of the National Cancer Institute
Publication statusPublished - 1998


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