TY - JOUR
T1 - KRAS-mutation status in relation to colorectal cancer survival
T2 - The joint impact of correlated tumour markers
AU - Phipps, A. I.
AU - Buchanan, D. D.
AU - Makar, K. W.
AU - Win, A. K.
AU - Baron, J. A.
AU - Lindor, N. M.
AU - Potter, J. D.
AU - Newcomb, P. A.
N1 - Funding Information:
This work was supported by the National Cancer Institute, National Institutes of Health under RFA no. CA-95-011, and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. In particular, this work was conducted through the Seattle Colorectal Cancer Family Registry (U01 CA074794) and through NCI grant R01CA076366. Paraffin-embedded tumour tissue for the Seattle Colorectal Cancer Family Registry was provided by The Jeremy Jass Memorial Pathology Bank. This publication was also supported by the NCI training grant R25CA94880 and by NCI grants K05CA152715 and K07CA172298. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the Cancer Family Registry.
PY - 2013/4/30
Y1 - 2013/4/30
N2 - 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.
AB - 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.
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U2 - 10.1038/bjc.2013.118
DO - 10.1038/bjc.2013.118
M3 - Article
C2 - 23511557
AN - SCOPUS:84877020358
SN - 0007-0920
VL - 108
SP - 1757
EP - 1764
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -