Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study

H. J N Andreyev, A. R. Norman, D. Cunningham, J. Oates, B. R. Dix, B. J. Iacopetta, J. Young, T. Walsh, R. Ward, N. Hawkins, M. Beranek, P. Jandik, R. Benamouzig, E. Jullian, P. Laurent-Puig, S. Olschwang, O. Muller, I. Hoffmann, H. M. Rabes, C. ZietzC. Troungos, C. Valavanis, S. T. Yuen, J. W C Ho, C. T. Croke, D. P. O'Donoghue, W. Giaretti, A. Rapallo, A. Russo, V. Bazan, M. Tanaka, K. Omura, T. Azuma, T. Ohkusa, T. Fujimori, Y. Ono, M. Pauly, C. Faber, R. Glaesener, A. F P M de Goeij, J. W. Arends, S. N. Andersen, T. Lövig, J. Breivik, G. Gaudernack, O. P F Clausen, P. De Angelis, G. I. Meling, T. O. Rognum, R. Smith, H. S. Goh, A. Font, R. Rosell, X. F. Sun, H. Zhang, J. Benhattar, L. Losi, J. Q. Lee, S. T. Wang, P. A. Clarke, S. Bell, P. Quirke, V. J. Bubb, J. Piris, N. R. Cruickshank, D. Morton, J. C. Fox, F. Al-Mulla, N. Lees, C. N. Hall, D. Snary, K. Wilkinson, D. Dillon, J. Costa, V. E. Pricolo, S. D. Finkelstein, J. S. Thebo, A. J. Senagore, S. A. Halter, S. Wadler, S. Malik, K. Krtolica, N. Urosevic

Research output: Contribution to journalArticle

645 Citations (Scopus)

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 incolorectal-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.

Original languageEnglish (US)
Pages (from-to)692-696
Number of pages5
JournalBritish Journal of Cancer
Volume85
Issue number5
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Mutation
Survival
Codon
Neoplasms
Valine
Glycine
Databases
Rectum
Adenoma
Colon
Multivariate Analysis
Genotype
Research Personnel
Genome
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Andreyev, H. J. N., Norman, A. R., Cunningham, D., Oates, J., Dix, B. R., Iacopetta, B. J., ... Urosevic, N. (2001). Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study. British Journal of Cancer, 85(5), 692-696. https://doi.org/10.1054/bjoc.2001.1964

Kirsten ras mutations in patients with colorectal cancer : The 'RASCAL II' study. / Andreyev, H. J N; 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.; Zietz, C.; Troungos, C.; Valavanis, C.; Yuen, S. T.; Ho, J. W C; Croke, C. T.; O'Donoghue, D. P.; Giaretti, W.; Rapallo, A.; Russo, A.; Bazan, V.; Tanaka, M.; Omura, K.; Azuma, T.; Ohkusa, T.; Fujimori, T.; Ono, Y.; Pauly, M.; Faber, C.; Glaesener, R.; Goeij, A. F P M de; Arends, J. W.; Andersen, S. N.; Lövig, T.; Breivik, J.; Gaudernack, G.; Clausen, O. P F; Angelis, P. De; Meling, G. I.; Rognum, T. O.; Smith, R.; Goh, H. S.; Font, A.; Rosell, R.; Sun, X. F.; Zhang, H.; Benhattar, J.; Losi, L.; Lee, J. Q.; Wang, S. T.; Clarke, P. A.; Bell, S.; Quirke, P.; Bubb, V. J.; Piris, J.; Cruickshank, N. R.; Morton, D.; Fox, J. C.; Al-Mulla, F.; Lees, N.; Hall, C. N.; Snary, D.; Wilkinson, K.; Dillon, D.; Costa, J.; Pricolo, V. E.; Finkelstein, S. D.; Thebo, J. S.; Senagore, A. J.; Halter, S. A.; Wadler, S.; Malik, S.; Krtolica, K.; Urosevic, N.

In: British Journal of Cancer, Vol. 85, No. 5, 01.09.2001, p. 692-696.

Research output: Contribution to journalArticle

Andreyev, HJN, Norman, AR, Cunningham, D, Oates, J, Dix, BR, Iacopetta, BJ, 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, HM, Zietz, C, Troungos, C, Valavanis, C, Yuen, ST, Ho, JWC, Croke, CT, O'Donoghue, DP, Giaretti, W, Rapallo, A, Russo, A, Bazan, V, Tanaka, M, Omura, K, Azuma, T, Ohkusa, T, Fujimori, T, Ono, Y, Pauly, M, Faber, C, Glaesener, R, Goeij, AFPMD, Arends, JW, Andersen, SN, Lövig, T, Breivik, J, Gaudernack, G, Clausen, OPF, Angelis, PD, Meling, GI, Rognum, TO, Smith, R, Goh, HS, Font, A, Rosell, R, Sun, XF, Zhang, H, Benhattar, J, 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, Thebo, JS, Senagore, AJ, Halter, SA, Wadler, S, Malik, S, Krtolica, K & Urosevic, N 2001, 'Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study', British Journal of Cancer, vol. 85, no. 5, pp. 692-696. https://doi.org/10.1054/bjoc.2001.1964
Andreyev HJN, Norman AR, Cunningham D, Oates J, Dix BR, Iacopetta BJ et al. Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study. British Journal of Cancer. 2001 Sep 1;85(5):692-696. https://doi.org/10.1054/bjoc.2001.1964
Andreyev, H. J N ; 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. ; Zietz, C. ; Troungos, C. ; Valavanis, C. ; Yuen, S. T. ; Ho, J. W C ; Croke, C. T. ; O'Donoghue, D. P. ; Giaretti, W. ; Rapallo, A. ; Russo, A. ; Bazan, V. ; Tanaka, M. ; Omura, K. ; Azuma, T. ; Ohkusa, T. ; Fujimori, T. ; Ono, Y. ; Pauly, M. ; Faber, C. ; Glaesener, R. ; Goeij, A. F P M de ; Arends, J. W. ; Andersen, S. N. ; Lövig, T. ; Breivik, J. ; Gaudernack, G. ; Clausen, O. P F ; Angelis, P. De ; Meling, G. I. ; Rognum, T. O. ; Smith, R. ; Goh, H. S. ; Font, A. ; Rosell, R. ; Sun, X. F. ; Zhang, H. ; Benhattar, J. ; Losi, L. ; Lee, J. Q. ; Wang, S. T. ; Clarke, P. A. ; Bell, S. ; Quirke, P. ; Bubb, V. J. ; Piris, J. ; Cruickshank, N. R. ; Morton, D. ; Fox, J. C. ; Al-Mulla, F. ; Lees, N. ; Hall, C. N. ; Snary, D. ; Wilkinson, K. ; Dillon, D. ; Costa, J. ; Pricolo, V. E. ; Finkelstein, S. D. ; Thebo, J. S. ; Senagore, A. J. ; Halter, S. A. ; Wadler, S. ; Malik, S. ; Krtolica, K. ; Urosevic, N. / Kirsten ras mutations in patients with colorectal cancer : The 'RASCAL II' study. In: British Journal of Cancer. 2001 ; Vol. 85, No. 5. pp. 692-696.
@article{c41d3fd94f4f4476aefee3711621fb74,
title = "Kirsten ras mutations in patients with colorectal cancer: The 'RASCAL II' study",
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 incolorectal-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.",
author = "Andreyev, {H. J N} and Norman, {A. R.} and D. Cunningham and J. Oates and Dix, {B. R.} and Iacopetta, {B. J.} and J. Young and T. Walsh and R. Ward and N. Hawkins and M. Beranek and P. Jandik and R. Benamouzig and E. Jullian and P. Laurent-Puig and S. Olschwang and O. Muller and I. Hoffmann and Rabes, {H. M.} and C. Zietz and C. Troungos and C. Valavanis and Yuen, {S. T.} and Ho, {J. W C} and Croke, {C. T.} and O'Donoghue, {D. P.} and W. Giaretti and A. Rapallo and A. Russo and V. Bazan and M. Tanaka and K. Omura and T. Azuma and T. Ohkusa and T. Fujimori and Y. Ono and M. Pauly and C. Faber and R. Glaesener and Goeij, {A. F P M de} and Arends, {J. W.} and Andersen, {S. N.} and T. L{\"o}vig and J. Breivik and G. Gaudernack and Clausen, {O. P F} and Angelis, {P. De} and Meling, {G. I.} and Rognum, {T. O.} and R. Smith and Goh, {H. S.} and A. Font and R. Rosell and Sun, {X. F.} and H. Zhang and J. Benhattar and L. Losi and Lee, {J. Q.} and Wang, {S. T.} and Clarke, {P. A.} and S. Bell and P. Quirke and Bubb, {V. J.} and J. Piris and Cruickshank, {N. R.} and D. Morton and Fox, {J. C.} and F. Al-Mulla and N. Lees and Hall, {C. N.} and D. Snary and K. Wilkinson and D. Dillon and J. Costa and Pricolo, {V. E.} and Finkelstein, {S. D.} and Thebo, {J. S.} and Senagore, {A. J.} and Halter, {S. A.} and S. Wadler and S. Malik and K. Krtolica and N. Urosevic",
year = "2001",
month = "9",
day = "1",
doi = "10.1054/bjoc.2001.1964",
language = "English (US)",
volume = "85",
pages = "692--696",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Kirsten ras mutations in patients with colorectal cancer

T2 - The 'RASCAL II' study

AU - Andreyev, H. J N

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 C

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 - Goeij, A. F P M de

AU - Arends, J. W.

AU - Andersen, S. N.

AU - Lövig, T.

AU - Breivik, J.

AU - Gaudernack, G.

AU - Clausen, O. P F

AU - Angelis, P. De

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 - 2001/9/1

Y1 - 2001/9/1

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 incolorectal-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.

AB - 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 incolorectal-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.

UR - http://www.scopus.com/inward/record.url?scp=0035444798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035444798&partnerID=8YFLogxK

U2 - 10.1054/bjoc.2001.1964

DO - 10.1054/bjoc.2001.1964

M3 - Article

C2 - 11531254

AN - SCOPUS:0035444798

VL - 85

SP - 692

EP - 696

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 5

ER -