Frequency and Clinical Impact of KRAS Mutations in Patients with Colorectal Cancer from the Middle East

Abstract

Background: Colorectal cancer (CRC) is a significant healthcare burden worldwide and in the Middle East (ME). KRAS mutation confers resistance to epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced CRC. Data regarding the rate of KRAS mutation from the ME are scattered and scarce. We aim to collect and review all sizable studies evaluating the frequency of KRAS mutations in CRC patients from the ME. Method:A Pubmed and Google Scholar search was conducted using keywords including KRAS, K-ras, colorectal cancer and Middle East, along with names of each ME country. Studies including over 90 patients were included in the review.Result: Eleven studies containing more than 90 patients were identified. Among all eleven studies, KRAS mutation rate ranged from 13 to 56%. Five studies reported KRAS mutation rate in M1 stage either exclusively or as part of subgroup analysis. In these studies, mutations were found in 8-45% of cases. KRAS mutations were associated with female gender, M1 stage and high CEA in 3, 2, and 1 studies respectively. Conclusion:There is a broad range of variability in KRAS mutation rate reported in different studies from the ME. This may have been due to small number of patients in the studies and lack of centralized testing for KRAS mutations. Larger and more coordinated studies from the ME population are required to ascertain the accuracy of KRAS mutation rate.

Metastatik Kolorektal Kanserli Hastaların RAS Mutasyon Durumuna Göre Klinik ve Patolojik Özellikleri

“…Ancak, CALGB/SWOG, FİRE-3, PEAK gibi en önemli KLİNİK çalışmalar çoğunlukla RAS mutasyon durumunun tedavi tercihini belirleyecek prediktif bir belirteç olup olmadığına yoğunlaşmışlardır 5 . Tanı anındaki RAS mutasyon durumuna göre KRK'li hastaların klinik ve patolojik özellikleri ile ilgili literatürde sınırlı çalışma ise vardır [6][7] . Biz bu çalışmada RAS gen mutasyon analizi yapılmış metastatik KRK'li hastalarda RAS mutant olan ve olmayan grupları; tümör lokalizasyonu, tanı anındaki metastaz yerleri, tümör belirteçleri ile ilişkisi, tümör diferansiyasyon derecesi ile ilişkisi ve genel sağkalım açısından karşılaştırmak istedik.…”

Molecular Spectrum of K-RAS Mutations in Colorectal Cancer Patients in Peshawar, Pakistan

“…These mutations lead to the continuous activation of signaling pathways such as PI3K/AKT and RAF/MEK/ERK, which are crucial for cell proliferation, migration, and survival (4, 5). Consequently, patients with CRC displaying these mutations often do not benefit from anti-epidermal growth factor receptor (EGFR) therapies, such as panitumumab and cetuximab, which are effective only in tumors expressing the wild-type KRAS gene (7). Given the significant impact of KRAS mutations on CRC prognosis and treatment outcomes, the current study aims to delineate the mutation patterns of the KRAS gene, specifically within codons 12 and 13, among colorectal cancer patients in Peshawar, Pakistan.…”