Περίληψη:
Researchers worldwide with information about the Kirsten ras (Ki-ras)
tumour genotype and outcome of patients with colorectal cancer were
invited to provide that data in a schematized format for inclusion in a
collaborative database called RASCAL (The Kirsten ras
in-colorectal-cancer collaborative group). Our results from 2721 such
patients have been presented previously and for the first time in any
common cancer, showed conclusively that different gene mutations have
different impacts on outcome, even when the mutations occur at the same
site on the genome. To explore the effect of Ki-ras mutations at
different stages of colorectal cancer, more patients were recruited to
the database, which was reanalysed when information on 4268 patients
from 42 centres in 21 countries had been entered. After predetermined
exclusion criteria were applied, data on 3439 patients were entered into
a multivariate analysis. This found that of the 12 possible mutations on
codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine
to valine, found in 8.6% of all patients, had a statistically
significant impact on failure-free survival (P = 0.004, HR 1.3) and
overall survival (P = 0.008, HR 1.29). This mutation appeared to have a
greater impact on outcome in Dukes’ C cancers (failure-free survival. P
= 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes’ B
tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P =
0.36, HR 1.15). Ki-ras mutations may occur early in the development of
pre-cancerous adenomas in the colon and rectum. However, this
collaborative study suggests that not only is the presence of a codon 12
glycine to valine mutation important for cancer progression but also
that it may predispose to more aggressive biological behaviour in
patients with advanced colorectal cancer. (C) 2001 Cancer Research
Campaign.
Συγγραφείς:
Andreyev, HJN
Norman, AR
Cunningham, D
Oates, J
Dix, BR
and Iacopetta, BJ
Young, J
Walsh, T
Ward, R
Hawkins, N
and Beranek, M
Jandik, P
Benamouzig, R
Jullian, E and
Laurent-Puig, P
Olschwang, S
Muller, O
Hoffmann, I and
Rabes, HM
Zietz, C
Troungos, C
Valavanis, C
Yuen, ST and
Ho, JWC
Croke, CT
O'Donoghue, DP
Giaretti, W
Rapallo, A
and Russo, A
Bazan, V
Tanaka, M
Omura, K
Azuma, T and
Ohkusa, T
Fujimori, T
Ono, Y
Pauly, M
Faber, C and
Glaesener, R
de Goeij, AFPM
Arends, JW
Andersen, SN and
Lovig, T
Breivik, J
Gaudernack, G
Clausen, OPF
De
Angelis, P
Meling, GI
Rognum, TO
Smith, R
Goh, HS and
Font, A
Rosell, R
Sun, XF
Zhang, H
Benhattar, J and
Losi, L
Lee, JQ
Wang, ST
Clarke, PA
Bell, S
Quirke,
P
Bubb, VJ
Piris, J
Cruickshank, NR
Morton, D
Fox,
JC
Al-Mulla, F
Lees, N
Hall, CN
Snary, D
Wilkinson,
K
Dillon, D
Costa, J
Pricolo, VE
Finkelstein, SD and
Thebo, JS
Senagore, AJ
Halter, SA
Wadler, S
Malik, S and
Krtolica, K
Urosevic, N
