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Exploring the Relationship Between KRAS, NRAS, and BRAF Mutations and Clinical Characteristics in Iranian Colorectal Cancer Patients

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Abstract

Background

Patients with colorectal cancer can benefit from anti-EGFR (epidermal growth factor receptor) therapy. However, this therapy is not effective for treating colorectal cancers with constitutive activating mutations in the KRAS, NRAS, and BRAF genes. Molecular analysis of tumor tissue frequently informs treatment decisions for colorectal cancer. This study aims to identify KRAS, NRAS, and BRAF mutations in Iranian patients diagnosed with colorectal cancer and to assess the prevalence of these mutations relative to the tumor differentiation stage within these populations.

Methods

From April 2018 to December 2022, 2000 specimens from patients with colorectal cancer were collected. Data on sex, age, and tumor differentiation stage were recorded for all samples. For mutation detection, the KRAS and NRAS exons (2, 3, and 4) were amplified using the Diatech kit, and a specific primer was used to amplify BRAF exon 15. Pyrosequencing was then performed.

Results

Analysis of samples revealed that 1105 specimens (55.3%) contained mutations in at least one of the screened genes. Among the genes studied, the highest occurrence was the KRAS mutation at 47.4%, followed by NRAS at 5.3% and BRAF at 2.7%. Most KRAS mutations were found in exon 2 (89.7%), with the G12D mutation being the most prevalent at 32% of cases. There was a significant difference in the rate of KRAS mutations in women (52.5%) compared to men (43.5%) (P =  0.02). For NRAS, the majority mutations were observed in exon 3 (76.2%), with the Q61H mutation being the most prevalent at 28.5% of cases. There were no significant associations between the clinicopathological parameters and mutations.

Conclusion

The study’s findings indicate a rising frequency of mutations in these genes in Iran, highlighting the need to screening mutations in the main exons of all three genes for effective colorectal cancer treatment strategies.

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Data Availability

Data were retrieved from public databases, as described in “Patients and Methods.”

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Acknowledgements

We thank Alpha Gen Laboratory for their assistance in different activities of the project.

Funding

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Authors and Affiliations

  1. Department of Cell and Molecular Biology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran

    Zahra Mosaferi & Azam Deilami

  2. Parasitology & Entomology Dept, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Majid Pirestani

  3. Department of Microbiology, School of Biology, College of Sciences, University of Tehran, Tehran, Iran

    Ehsan Arefian

  4. Pediatric Cell and Gene Therapy Research Center, & Tissue Research Institute, Tehran University of Medical Sciences, GeneTehran, Cell, Iran

    Ehsan Arefian

  5. National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

    Goli Gojani

  6. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Nastaran Kavousinasab

  7. Department of Chemistry, Faculty of Chemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran

    Parto Karimi

  8. Department of Cell and Molecular Biology, School of Biology, College of Sciences, University of Tehran, P. O. Box, Tehran, 14155-6455, Iran

    Zahra Abrehdari-Tafreshi

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Contributions

ZM, EA, MP, ZAT performed all experiments, prepared the figures, and drafted the manuscript. ZAT, ZM, GG, PK, NK, AD participated in data analyses and interpretation results. ZAT, ZM designed the study. All authors have read and approved the final manuscript.

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Correspondence to Zahra Abrehdari-Tafreshi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of Tehran University Ethical Committee (approval ID: IR.UT.SCIENCE. REC.1400007). In this study, individual consent was taken from patients.

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Mosaferi, Z., Pirestani, M., Arefian, E. et al. Exploring the Relationship Between KRAS, NRAS, and BRAF Mutations and Clinical Characteristics in Iranian Colorectal Cancer Patients. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-024-01064-0

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