In a study published in the British Journal of Cancer''s September issue, members of the Kirsten-ras in colorectal-cancer collaborative group have reported findings from their collaborative database RASCAL.
The group invited researchers worldwide with information on both the Kirsten ras (Ki-ras) tumor genotype and outcome of patients with colorectal cancer, to contribute their data in a schematized format for inclusion in the RASCAL database.
The RASCAL research group had previously presented results from 2721 such patients and were able to show conclusively for the first time in any common cancer, that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome.
In order to further this research, a greater number of cases were added to the database and the effect of Ki-ras mutations at different stages of colorectal cancer was explored.
The database was reanalyzed when it contained information on 4268 patients from 42 centers in 21 countries.
After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis.
|Ki-ras, codon 12 glycine to valine:|
- important in colorectal cancer progression
|British Journal of Cancer|
The research group found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation had a statistically significant impact on failure-free survival and overall survival.
The critical mutation, present on codon 12, and leading to substitution of valine for glycine, was found in almost 9% of patients.
This mutation appears to have a greater impact on outcome in Dukes' C cancers than in Dukes' B tumors.
Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum.
However, the RASCAL 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 behavior in patients with advanced colorectal cancer.