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

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

Coral skeletons provide historical evidence of phosphorus runoff on the Great Barrier Reef

Recently, the inshore reefs of the Great Barrier Reef have declined rapidly because of deteriorating water quality. Increased catchment runoff is one potential culprit. The impacts of land-use on coral growth and reef health however are largely circumstantial due to limited long-term data on water quality and reef health. Here we use a 60 year coral core record to show that phosphorus contained in the skeletons (P/Ca) of long-lived, near-shore Porites corals on the Great Barrier Reef correlates with annual records of fertiliser application and particulate phosphorus loads in the adjacent catchment. Skeletal P/Ca also correlates with Ba/Ca, a proxy for fluvial sediment loading, again linking near-shore phosphorus records with river runoff. Coral core records suggest that phosphorus levels increased 8 fold between 1949 and 2008 with the greatest levels coinciding with periods of high fertiliser-phosphorus use. Periods of high P/Ca correspond with intense agricultural activity and increased fertiliser application in the river catchment following agricultural expansion and replanting after cyclone damage. Our results demonstrate how coral P/Ca records can be used to assess terrestrial nutrient loading of vulnerable near-shore reefs

Kisten ras mutations in patients with colorectal cancer: the “RASCAL II” study.

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 predispose to more aggressive biological behaviour in patients with advanced colorectal cancer