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Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.
Br J Cancer. 2001 Sep 01; 85(5):692-6.BJ

Abstract

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.

Authors+Show Affiliations

Department of Medicine & Therapeutics, Imperial College School of Medicine, Chelsea & Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UKNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11531254

Citation

Andreyev, H J., et al. "Kirsten Ras Mutations in Patients With Colorectal Cancer: the 'RASCAL II' Study." British Journal of Cancer, vol. 85, no. 5, 2001, pp. 692-6.
Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer. 2001;85(5):692-6.
Andreyev, H. J., Norman, A. R., Cunningham, D., Oates, J., Dix, B. R., Iacopetta, B. J., Young, J., Walsh, T., Ward, R., Hawkins, N., Beranek, M., Jandik, P., Benamouzig, R., Jullian, E., Laurent-Puig, P., Olschwang, S., Muller, O., Hoffmann, I., Rabes, H. M., ... Urosevic, N. (2001). Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. British Journal of Cancer, 85(5), 692-6.
Andreyev HJ, et al. Kirsten Ras Mutations in Patients With Colorectal Cancer: the 'RASCAL II' Study. Br J Cancer. 2001 Sep 1;85(5):692-6. PubMed PMID: 11531254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. AU - Andreyev,H J, AU - Norman,A R, AU - Cunningham,D, AU - Oates,J, AU - Dix,B R, AU - Iacopetta,B J, AU - Young,J, AU - Walsh,T, AU - Ward,R, AU - Hawkins,N, AU - Beranek,M, AU - Jandik,P, AU - Benamouzig,R, AU - Jullian,E, AU - Laurent-Puig,P, AU - Olschwang,S, AU - Muller,O, AU - Hoffmann,I, AU - Rabes,H M, AU - Zietz,C, AU - Troungos,C, AU - Valavanis,C, AU - Yuen,S T, AU - Ho,J W, AU - Croke,C T, AU - O'Donoghue,D P, AU - Giaretti,W, AU - Rapallo,A, AU - Russo,A, AU - Bazan,V, AU - Tanaka,M, AU - Omura,K, AU - Azuma,T, AU - Ohkusa,T, AU - Fujimori,T, AU - Ono,Y, AU - Pauly,M, AU - Faber,C, AU - Glaesener,R, AU - de Goeij,A F, AU - Arends,J W, AU - Andersen,S N, AU - Lövig,T, AU - Breivik,J, AU - Gaudernack,G, AU - Clausen,O P, AU - De Angelis,P D, AU - Meling,G I, AU - Rognum,T O, AU - Smith,R, AU - Goh,H S, AU - Font,A, AU - Rosell,R, AU - Sun,X F, AU - Zhang,H, AU - Benhattar,J, AU - Losi,L, AU - Lee,J Q, AU - Wang,S T, AU - Clarke,P A, AU - Bell,S, AU - Quirke,P, AU - Bubb,V J, AU - Piris,J, AU - Cruickshank,N R, AU - Morton,D, AU - Fox,J C, AU - Al-Mulla,F, AU - Lees,N, AU - Hall,C N, AU - Snary,D, AU - Wilkinson,K, AU - Dillon,D, AU - Costa,J, AU - Pricolo,V E, AU - Finkelstein,S D, AU - Thebo,J S, AU - Senagore,A J, AU - Halter,S A, AU - Wadler,S, AU - Malik,S, AU - Krtolica,K, AU - Urosevic,N, PY - 2001/9/5/pubmed PY - 2001/10/5/medline PY - 2001/9/5/entrez SP - 692 EP - 6 JF - British journal of cancer JO - Br. J. Cancer VL - 85 IS - 5 N2 - 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. SN - 0007-0920 UR - https://www.unboundmedicine.com/medline/citation/11531254/Kirsten_ras_mutations_in_patients_with_colorectal_cancer:_the_'RASCAL_II'_study_ L2 - http://dx.doi.org/10.1054/bjoc.2001.1964 DB - PRIME DP - Unbound Medicine ER -