© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 675-684, Copyright © 1998 by Oxford University Press
HJ Andreyev, AR Norman, D Cunningham, JR Oates and PA Clarke
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<.001) and death (P = .004). In particular, any mutation of guanine
(G) to thymine (T) but not to adenine (A) or to cytosine (C) increased the
risk of recurrence (P = .006) and death (P<.001). When individual,
specific mutations were evaluated, only valine codon 12 was found to convey
an independent, increased risk of recurrence (P = .007) and death (P =
.004). CONCLUSIONS: Ki-ras mutations are associated with increased risk of
relapse and death, but some mutations are more aggressive than others.
ARTICLES
Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study
Department of Medicine, Royal Marsden Hospital, Institute of Cancer Research, Sutton, Surrey, UK.
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