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

A. I. Phipps, D. D. Buchanan, K. W. Makar, A. K. Win, J. A. Baron, Noralane Morey Lindor, J. D. Potter, P. A. Newcomb

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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.

Original languageEnglish (US)
Pages (from-to)1757-1764
Number of pages8
JournalBritish Journal of Cancer
Volume108
Issue number8
DOIs
StatePublished - Apr 30 2013

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Tumor Biomarkers
Colorectal Neoplasms
Joints
Microsatellite Instability
Mutation
Survival
Confidence Intervals
Neoplasms
ras Genes
Exons

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

KRAS-mutation status in relation to colorectal cancer survival : The joint impact of correlated tumour markers. / Phipps, A. I.; Buchanan, D. D.; Makar, K. W.; Win, A. K.; Baron, J. A.; Lindor, Noralane Morey; Potter, J. D.; Newcomb, P. A.

In: British Journal of Cancer, Vol. 108, No. 8, 30.04.2013, p. 1757-1764.

Research output: Contribution to journalArticle

Phipps, AI, Buchanan, DD, Makar, KW, Win, AK, Baron, JA, Lindor, NM, Potter, JD & Newcomb, PA 2013, 'KRAS-mutation status in relation to colorectal cancer survival: The joint impact of correlated tumour markers', British Journal of Cancer, vol. 108, no. 8, pp. 1757-1764. https://doi.org/10.1038/bjc.2013.118
Phipps, A. I. ; Buchanan, D. D. ; Makar, K. W. ; Win, A. K. ; Baron, J. A. ; Lindor, Noralane Morey ; Potter, J. D. ; Newcomb, P. A. / KRAS-mutation status in relation to colorectal cancer survival : The joint impact of correlated tumour markers. In: British Journal of Cancer. 2013 ; Vol. 108, No. 8. pp. 1757-1764.
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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.",
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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, Noralane Morey

AU - Potter, J. D.

AU - Newcomb, P. A.

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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DO - 10.1038/bjc.2013.118

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