KRAS-mutation status in relation to colorectal cancer survival: The joint impact of correlated tumour markers
Open accessAbstract
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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The median overall survival for each mutation type in this cohort was consistent with previously reported values, indicating that the cohort is representative of the metastatic colorectal cancer population and that the results reflect clinical practice.
“Median OS for each type of mutation (i.e., KRAS exon 2 wild-type, KRAS exon 2 mutant, and BRAF V600E mutant) was consistent with that reported previously [14,15], indicating that our cohort was representative of the mCRC population and that the results presented here reflect prognosis in clinical practice.”
From The Prognostic Impact of <i>KRAS</i> G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study (2021) · cites this paper as [14]
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- Authors
- Phipps, A. I., Buchanan, D. D., Makar, K. W., Win, A. K., Baron, J. A., Lindor, N. M., Potter, J. D., & Newcomb, P. A.
- Affiliations
- Fred Hutch Cancer Center (US)
- QIMR Berghofer Medical Research Institute (AU)
- The University of Melbourne (AU)
- University of North Carolina at Chapel Hill (US)
- Mayo Clinic (US)
- Corresponding author
- Phipps, A I
- Venue
- British Journal of Cancer
- Published
- 2013-03-19
- Volume
- 108
- Issue
- 8
- Pages
- 1757-1764
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3668469
- OpenAlex
- W1983040612
- Cited by
- 238
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 10 · 2023: 15 · 2022: 14 · 2021: 22 · 2020: 21 · 2019: 24 · 2018: 21 · 2017: 31 · 2016: 21 · 2015: 24 · 2014: 21 · 2013: 5
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- authors@Fred Hutch (Fred Hutchinson Cancer Research Center) (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- UNC Libraries
- Funders
- National Institutes of Health (-95-011)
- National Cancer Institute (K05CA152715, U01CA074794, U24CA074794, R01CA076366, K07CA172298, CA074794, # CA-95-011, R25CA094880)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- KRAS mutation, colorectal cancer, prognosis, survival, BRAF V600E mutation, microsatellite instability, disease-specific survival, overall survival, tumor markers, tumor stage
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Mutation, Genes, ras, Washington, Colorectal Neoplasms, Survival Rate, SEER Program, Young Adult
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