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Br J Cancer. 2013 Apr 30;108(8):1757-64. doi: 10.1038/bjc.2013.118. Epub 2013 Mar 19.

KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers.

Author information

1
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA. aphipps@fhcrc.org

Abstract

BACKGROUND:

Mutations in the Kirsten Ras (KRAS) oncogene are common in colorectal cancer (CRC). The role of KRAS-mutation status as a prognostic factor, however, is unclear. We evaluated the relationship between KRAS-mutation status and CRC survival, considering heterogeneity in this association by tumour and patient characteristics.

METHODS:

The population-based study included individuals diagnosed with CRC between 1998-2007 in Western Washington State. Tumour specimens were tested for KRAS exon 2 mutations, the BRAF p.V600E mutation, and microsatellite instability (MSI). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between KRAS-mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumour site, stage, and MSI. We conducted additional analyses combining KRAS-mutation, BRAF-mutation, and MSI status.

RESULTS:

Among 1989 cases, 31% had KRAS-mutated CRC. Kirsten Ras (KRAS)-mutated CRC was associated with poorer disease-specific survival (HR=1.37, 95% CI: 1.13-1.66). This association was not evident in cases who presented with distant-stage CRC. Cases with KRAS-wild-type/BRAF-wild-type/MSI-high CRC had the most favourable prognosis; those with CRC exhibiting a KRAS- or BRAF-mutation and no MSI had the poorest prognosis. Patterns were similar for overall survival.

CONCLUSION:

Kirsten Ras (KRAS)-mutated CRC was associated with statistically significantly poorer survival after diagnosis than KRAS-wild-type CRC.

PMID:
23511557
PMCID:
PMC3668469
DOI:
10.1038/bjc.2013.118
[Indexed for MEDLINE]
Free PMC Article
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