KRAS mutational status in Japanese patients with colorectal cancer: Results from a nationwide, multicenter, cross-sectional study
Abstract
OBJECTIVE: KRAS gene mutations are a useful predictive factor for the efficacy of anti-epidermal growth factor receptor therapeutics. Since there were no large-scale studies among Asian populations, we designed an observational nationwide study in Japan. METHODS: Formalin-fixed paraffin-embedded tissue blocks or sections from primary or metastatic lesions were obtained from patients registered between 2009 and 2010 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors. RESULTS: We analyzed 5790 eligible samples out of 5887 registered. The overall KRAS mutation rate was 37.6%, with 29.9% in codon 12 and 7.7% in codon 13, and wild type was 62.4%. A significant relationship with the KRAS mutation rate was found for gender, age, the year that the sample was prepared and the site of the primary lesion. CONCLUSION: The KRAS mutation rate of Japanese colorectal cancer patients was 37.6%. Gender, age, the site of the primary lesion and the year that the sample was prepared were independent risk factors for KRAS mutations.
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KRAS mutations are detected in approximately 35-45% of patients with locally advanced rectal cancer, with no significant differences in KRAS status between colorectal and rectal cancers.
“KRAS mutations are detected in approximately 35–45% of patients with locally advanced rectal cancer, with no significant differences in KRAS status between colorectal and rectal cancers [45]”
From The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives (2025) · cites this paper as [45]
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 [45]
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 [45]
Cites
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132 · see citing works
Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer
Van Cutsem, E., Köhne, C.-H., Hitre, E., Zaluski, J., Chang Chien, C.-R., Makhson, A., D'Haens, G., Pintér, T., Lim, R., Bodoky, G., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805019 · Cited by 3,877 · see citing works
<i>K-ras</i> Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622 · see citing works
Amado, R. G., Wolf, M., Peeters, M., Van Cutsem, E., Siena, S., Freeman, D. J., Juan, T., Sikorski, R., Suggs, S., Radinsky, R., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.7116 · Cited by 3,207 · see citing works
Hyperactive Ras in developmental disorders and cancer
Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583 · see citing works
Roth, A. D., Tejpar, S., Delorenzi, M., Yan, P., Fiocca, R., Klingbiel, D., Dietrich, D., Biesmans, B., Bodoky, G., Barone, C., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.3452 · Cited by 1,178 · see citing works
Kirsten ras mutations in patients with colorectal cancer: The multicenter “RASCAL” study
Andreyev, H. J. N., Norman, A. R., Clarke, P. A., Cunningham, D., & Oates, J. R. (1998) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/90.9.675 · Cited by 748 · see citing works
Revised TN Categorization for Colon Cancer Based on National Survival Outcomes Data
Gunderson, L. L., Jessup, J. M., Sargent, D. J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.0952 · Cited by 620 · see citing works
Konishi, M., Kikuchi‐Yanoshita, R., Tanaka, K., Muraoka, M., Onda, A., Okumura, Y., Kishi, N., Iwama∥, T., Mori, T., Koike, M., et al. (1996) · Gastroenterology · doi:10.1053/gast.1996.v111.pm8690195 · Cited by 440 · see citing works
Loupakis, F., Pollina, L., Stasi, I., Ruzzo, A., Scartozzi, M., Santini, D., Masi, G., Graziano, F., Cremolini, C., Rulli, E., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.2796 · Cited by 403 · see citing works
Barault, L., Veyrie, N., Jooste, V., Corre, D. L., Chapusot, C., Ferraz, J., Lièvre, A., Cortet, M., Bouvier, A., Rat, P., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.23388 · Cited by 345 · see citing works
Samowitz, W. S., Curtin, K. P., Schaffer, D., Robertson, M. A., Leppert, M., & Slattery, M. L. (2000) · PubMed · Cited by 320 · see citing works
van Krieken, J. H., Jung, A., Kirchner, T., Carneiro, F., Seruca, R., Bosman, F. T., Quirke, P., Fléjou, J., Hansen, T. P., Hertogh, G. D., et al. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-008-0665-y · Cited by 289 · see citing works
Santini, D., Loupakis, F., Vincenzi, B., Floriani, I., Stasi, I., Canestrari, E., Rulli, E., Maltese, P. E., Andreoni, F., Masi, G., et al. (2008) · The Oncologist · doi:10.1634/theoncologist.2008-0181 · Cited by 234 · see citing works
Fujiwara, T., Stolker, J. M., Watanabe, T., et al. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65651-9 · Cited by 190 · see citing works
Self-citationDNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer
Kawakami, K., Ruszkiewicz, A. R., Bennett, G., Moore, J., Grieu, F., Watanabe, G., & Iacopetta, B. M. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602940 · Cited by 132 · see citing works
Hiraoka, S., Kato, J., Tatsukawa, M., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.04.027 · Cited by 88 · see citing works
Abubaker, J. A., Bavi, P. P., Al‐Haqawi, W., Sultana, M., Al-harbi, S., Al-Sanea, N. A., Abduljabbar, A. S., Ashari, L. H. S., Alhomoud, S. J., Al‐Dayel, F., et al. (2009) · The Journal of Pathology · doi:10.1002/path.2625 · Cited by 86 · see citing works
Watanabe, T., Kobunai, T., Yamamoto, Y., Matsuda, K., Ishihara, S., Nozawa, K., Iinuma, H., Shibuya, H., & Eshima, K. (2011) · Diseases of the Colon & Rectum · doi:10.1097/dcr.0b013e31821d37a3 · Cited by 82 · see citing works
Self-citationCetuximab for the first-line treatment of metastatic colorectal cancer
Meads, C., Round, J. A., Tubeuf, S., Moore, D., Pennant, M. E., Bayliss, S. E., & McCabe, C. J. (2010) · Health Technology Assessment · doi:10.3310/hta14suppl1/01 · Cited by 80 · see citing works
NICE - National Institute for Health and Clinical Excellence
Gouveia, C. A. D. S. (2009) · Revista Portuguesa de Clínica Geral · doi:10.32385/rpmgf.v25i2.10623 · Cited by 77 · see citing works
K‐ras point mutations in human colorectal carcinomas: Relation to aneuploidy and metastasis
Suchy, B., Zietz, C., & Rabes, H. M. (1992) · International Journal of Cancer · doi:10.1002/ijc.2910520107 · Cited by 76 · see citing works
Kaku, E., Oda, Y., Murakami, Y., et al. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.03.018 · Cited by 76 · see citing works
Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis
Umetani, N., Sasaki, S., Masaki, T., et al. (2000) · British Journal of Cancer · doi:10.1054/bjoc.1999.0869 · Cited by 55 · see citing works
Zlobec, I., Molinari, F., Kovac, M., Bihl, M., Altermatt, H. J., Diebold, J., Frick, H., Germer, M., Horcic, M., Montani, M., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6605452 · Cited by 54 · see citing works
Mukawa, K., Fujii, S., Takeda, J., et al. (2005) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2005.03897.x · Cited by 26 · see citing works
Bando, H., Tsuchihara, K., Yoshino, T., et al. (2010) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyq216 · Cited by 21 · see citing works
Self-citationHorii, J., Hiraoka, S., Kato, J., Saito, S., Harada, K., Fujita, H., Kaji, E., & Yamamoto, K. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01140.x · Cited by 10 · see citing works
Ferreira, C. G., Zalcberg-Renault, I., Vieira, F. M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.15_suppl.3614 · Cited by 6 · see citing works
Zhu, G.-G., Kauppila, A., Risteli, L., Mäkinen, M., Stenbäck, F., & Risteli, J. (1995) · Cancer · doi:10.1002/1097-0142(19950215)75:4
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Yoshino, T., Arnold, D., Taniguchi, H., Pentheroudakis, G., Yamazaki, K., Xu, R.-H., Kim, T. W., Ismail, F., Tan, I. B., Yeh, K.-H., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdx738 · Cited by 573 · see citing works
Self-citationKRAS: From undruggable to a druggable Cancer Target
Uprety, D., & Adjei, A. A. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102070 · Cited by 271 · see citing works
Takeda, M., Yoshida, S., Inoue, T., Sekido, Y., Hata, T., Hamabe, A., Ogino, T., Miyoshi, N., Uemura, M., Yamamoto, H., et al. (2025) · Cancers · doi:10.3390/cancers17030428 · Cited by 82 · see citing works
- Authors
- Watanabe, T., Yoshino, T., Uetake, H., Yamazaki, K., Ishiguro, M., Kurokawa, T., Saijo, N., Ohashi, Y., & Sugihara, K.
- Affiliations
- The University of Tokyo (JP)
- National Cancer Center Hospital East (JP)
- Tokyo Medical and Dental University (JP)
- Shizuoka Cancer Center (JP)
- Keio University (JP)
- Japanese Society of Medical Oncology (JP)
- ORCID
- Venue
- Japanese Journal of Clinical Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-05-08
- Volume
- 43
- Issue
- 7
- Pages
- 706-712
- ISSN
- 0368-2811 (ISSN-L)
- 1465-3621
- OpenAlex
- W2152297937
- Cited by
- 46
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 6 · 2013: 1
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Japanese Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- KRAS mutation, colorectal cancer, mutation frequency, codon 12, codon 13, risk factors, Japanese patients, anti-EGFR therapy, primary tumor site, age and gender differences
- MeSH terms
- Adult, Age Factors, Aged, Analysis of Variance, Cross-Sectional Studies, Female, Humans, Japan, Male, Middle Aged, Mutation, Proto-Oncogene Proteins, Risk Factors, Sex Factors, Colorectal Neoplasms, Logistic Models, Proto-Oncogene Proteins p21(ras), ras Proteins, Asian People
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