A1 Refereed original research article in a scientific journal

KRAS and NRAS mutations in Nordic population-based and real-world metastatic colorectal cancer cohorts



Authors: Österlund, Emerik; Ristimäki, Ari; Nunes, Luís; Kytölä, Soili; Aho, Sonja; Heervä, Eetu; Uutela, Aki; Lehtomäki, Kaisa; Stedt, Hanna; Halonen, Päivi; Kontiainen, Joel; Muhonen, Timo; Kallio, Raija; Sundström, Jari; Ålgars, Annika; Ristamäki, Raija; Nieminen, Lasse; Sorbye, Halfdan; Pfeiffer, Per; Salminen, Tapio; Nordin, Arno; Lamminmäki, Annamarja; Mäkinen, Markus J.; Sjöblom, Tobias; Isoniemi, Helena; Glimelius, Bengt; Osterlund, Pia

Publisher: Nature Publishing Group

Publication year: 2025

Journal:: BJC Reports

Article number: 72

Volume: 3

eISSN: 2731-9377

DOI: https://doi.org/10.1038/s44276-025-00188-5

Web address : https://doi.org/10.1038/s44276-025-00188-5

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/504932970


Abstract
Background

KRAS and NRAS mutations (mt) are drivers in metastatic colorectal cancer (mCRC). We studied frequencies, characteristics, treatments, and outcomes of different KRASmt and NRASmt in population-based and real-world settings.

Methods

Three Nordic cohorts were combined and molecularly characterised for KRAS, NRAS, and BRAF-V600E hotspot mutations.

Results

Of 2649 mCRC patients, 2118 were molecularly classified. KRASmt were seen in 49%, NRASmt in 4%, RAS&BRAFwt in 33%, and BRAF-V600Emt in 14%. No differences in clinical characteristics were observed between KRASmt and NRASmt. Median overall survival (OS) was longest among RAS&BRAFwt, intermediate among KRASmt and NRASmt, and shortest among BRAF-V600Emt (28.3 vs 21.4 vs 26.3 vs 9.2 months, respectively). Among the eight most common KRASmt, the only clinical difference was that KRAS-G12S had more distant lymph node metastases (38% vs 18–27%, p = 0.041). KRAS-G12S had shorter OS than KRAS-G12V, KRAS-G12C, KRAS-G12A, and KRAS-G13D. The differences were smaller in treatment groups but withstood in multivariable models. The three most common NRASmt did not differ clinically.

Conclusion

KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.

Funding information in the publication: 
This RAXO-study was supported by Finska Läkaresällskapet (2016, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025), The Finnish Cancer Foundation (2019–2020, 2021, 2022–2023, 2024), Relander’s foundation (2020–2022), the Competitive State Research Financing of the Expert Responsibility Area of Tampere, Helsinki, Turku, Kuopio, Oulu, and Satakunta Hospitals (2012, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025), Tampere University Hospital Fund (Tukisäätiö 2019, 2020, 2023 and OOO-project 2020, 2022), Helsinki University Hospital research fund (2019, 2020, 2021, 2022, 2023, 2024), and the infrastructure with the database and study nurses partly supported by pharmaceutical companies: Amgen—unrestricted grant (2012–2020, 2023), Eli Lilly and Company (2012–2017), Merck KGaA (2012–2020), Roche Oy (2012–2020), Sanofi (2012–2017), and Servier—unrestricted grant (2016–2024). The PRCRC-study was supported by the Swedish Cancer Society (CAN 2016/447 and CAN 2018/1165). The NGS analyses in the Uppsala region cohort were supported by the Swedish Cancer Society (22 2054 Pj 01H), Lions Cancerforskningsfond Mellansverige, and Amgen. The funding sources had no role in the design and conduct of the study, collection, analysis and interpretation of the data or decision to submit the manuscript for publication. Open access funding provided by Uppsala University.


Last updated on 2025-24-10 at 15:16