@article{3080631, title = "Kirsten ras mutations in patients with colorectal cancer: the `RASCAL II' study", author = "Andreyev, HJN and Norman, AR and Cunningham, D and Oates, J and Dix, BR and and Iacopetta, BJ and Young, J and Walsh, T and Ward, R and Hawkins, N and and Beranek, M and Jandik, P and Benamouzig, R and Jullian, E and and Laurent-Puig, P and Olschwang, S and Muller, O and Hoffmann, I and and Rabes, HM and Zietz, C and Troungos, C and Valavanis, C and Yuen, ST and and Ho, JWC and Croke, CT and O'Donoghue, DP and Giaretti, W and Rapallo, A and and Russo, A and Bazan, V and Tanaka, M and Omura, K and Azuma, T and and Ohkusa, T and Fujimori, T and Ono, Y and Pauly, M and Faber, C and and Glaesener, R and de Goeij, AFPM and Arends, JW and Andersen, SN and and Lovig, T and Breivik, J and Gaudernack, G and Clausen, OPF and De and Angelis, P and Meling, GI and Rognum, TO and Smith, R and Goh, HS and and Font, A and Rosell, R and Sun, XF and Zhang, H and Benhattar, J and and Losi, L and Lee, JQ and Wang, ST and Clarke, PA and Bell, S and Quirke, and P and Bubb, VJ and Piris, J and Cruickshank, NR and Morton, D and Fox, and JC and Al-Mulla, F and Lees, N and Hall, CN and Snary, D and Wilkinson, and K and Dillon, D and Costa, J and Pricolo, VE and Finkelstein, SD and and Thebo, JS and Senagore, AJ and Halter, SA and Wadler, S and Malik, S and and Krtolica, K and Urosevic, N", journal = "British Journal of Cancer", year = "2001", volume = "85", number = "5", pages = "692-696", publisher = "Nature Publishing Group", issn = "0007-0920, 1532-1827", doi = "10.1054/bjoc.2001.1964", 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. (C) 2001 Cancer Research Campaign." }