Kirsten ras mutations in patients with colorectal cancer: The multicenter “RASCAL” study
Abstract
BACKGROUND: Kirsten ras (Ki-ras) gene mutations occur early in the progression of colorectal adenoma to carcinoma. The aim of this collaborative study was to clarify the association between Ki-ras mutations, patient outcome, and tumor characteristics by use of data from colorectal cancer patients worldwide. METHODS: Investigators who had published data on Ki-ras and colorectal cancer were invited to complete a questionnaire for each patient entered into a database. Two-sided statistical tests were used to analyze data. RESULTS: Patients (n = 2721) were recruited from 22 groups in 13 countries. Mutations of Ki-ras codon 12 (wild type = GGT = glycine) or codon 13 (wild type = GGC = glycine) were detected in 37.7% of the tumors; 80.8% (584 of 723) of all the specified mutations occurred in codon 12, and 78.1% (565 of 723) of all the specified mutations were at the second base of either codon. Mutations were not associated with sex, age, tumor site, or Dukes' stage. Mutation rates seen in patients with sporadic tumors were comparable to those observed in patients with a predisposing cause for their cancer. Poorly differentiated tumors were less frequently mutated (P = .002). Multivariate analysis suggested that the presence of a mutation increased risk of recurrence (P<.001) and death (P = .004). In particular, any mutation of guanine (G) to thymine (T) but not to adenine (A) or to cytosine (C) increased the risk of recurrence (P = .006) and death (P<.001). When individual, specific mutations were evaluated, only valine codon 12 was found to convey an independent, increased risk of recurrence (P = .007) and death (P = .004). CONCLUSIONS: Ki-ras mutations are associated with increased risk of relapse and death, but some mutations are more aggressive than others.
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The frequency of KRAS exon 2 (codons 12, 13) mutations is approximately 35-40% in colorectal cancer, with no differences observed between reports from Western countries and Japan.
“The frequency of KRAS exon 2 (codons 12, 13) mutations is approximately 35–40% in colorectal cancer, with no differences observed between reports from Western countries and Japan (Table 1).”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [46]
KRAS mutations are found in 30-40% of colorectal cancer cases.
“Found in 30–40% of cases”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [46]
Validating RAS wild-type status, including codons 12, 13, 59, 61, 117, and 146 in exons 2, 3, and 4, is essential for establishing treatment strategies for advanced colorectal cancer.
“validating RAS wild-type status, including codons 12, 13, 59, 61, 117, and 146 in exons 2, 3, and 4, is essential for establishing treatment strategies for advanced colorectal cancer (CRC) [46,48]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [46]
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- Authors
- Andreyev, H. J. N., Norman, A. R., Clarke, P. A., Cunningham, D., & Oates, J. R.
- Affiliations
- Royal Marsden Hospital (GB)
- Institute of Cancer Research (GB)
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-05-06
- Volume
- 90
- Issue
- 9
- Pages
- 675-684
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2136509556
- Cited by
- 748
- References
- 39
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 7 · 2023: 16 · 2022: 13 · 2021: 28 · 2020: 29 · 2019: 22 · 2018: 12 · 2017: 23 · 2016: 31 · 2015: 42 · 2014: 51 · 2013: 43 · 2012: 52
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- 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
- Ki-ras mutation, colorectal cancer, codon 12 mutation, codon 13 mutation, tumor recurrence, cancer mortality, tumor differentiation, prognostic factors
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Predictive Value of Tests, Prognosis, Genes, ras, Colorectal Neoplasms, Multivariate Analysis, Odds Ratio, Survival Analysis, Disease-Free Survival
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