Regional and Gender-Based Distribution of KRAS Mutations in Metastatic Colorectal Cancer Patients in Turkey: An Observational Study
Nurullah Ilhan,
Faysal Dane,
Erdem Goker,
Kazım Uygun,
Bülent Orhan,
Kerem Okutur,
İlkay Tuğba Ünek,
Abdurrahman Işıkdoğan,
Ahmet Bilici,
Nurullah Zengin,
Necati Alkış,
İdris Yücel,
Hatice Odabaş,
Berna Ömür Öksüzoğlu,
Akif Doğan,
Hande Nur Erölmez,
Mahmut Gümüş
Affiliations
Nurullah Ilhan
Department of Medical Oncology, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, 34785 Istanbul, Turkey
Faysal Dane
Department of Medical Oncology, Faculty of Medicine, Marmara University, 34865 Istanbul, Turkey
Erdem Goker
Department of Medical Oncology, Faculty of Medicine, Ege University, 35040 İzmir, Turkey
Kazım Uygun
Department of Medical Oncology, Faculty of Medicine, Kocaeli University, 41285 Kocaeli, Turkey
Bülent Orhan
Department of Medical Oncology, Acıbadem Bursa Hospital, 16210 Bursa, Turkey
Kerem Okutur
Department of Medical Oncology, Samsun Training and Research Hospital, University of Health Sciences, 55090 Samsun, Turkey
İlkay Tuğba Ünek
Department of Medical Oncology, İzmir Tepecik Training and Research Hospital, University of Health Sciences, 06080 İzmir, Turkey
Abdurrahman Işıkdoğan
Department of Medical Oncology, Faculty of Medicine, Dicle University, 21280 Diyarbakır, Turkey
Ahmet Bilici
Department of Medical Oncology, Şişli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, 34096 Istanbul, Turkey
Nurullah Zengin
Department of Medical Oncology, Ankara Numune Training and Research Hospital, University of Health Sciences, 06100 Ankara, Turkey
Necati Alkış
Department of Medical Oncology, Ankara Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, 06200 Ankara, Turkey
İdris Yücel
Department of Medical Oncology, Faculty of Medicine, Ondokuz Mayıs University, 55270 Samsun, Turkey
Hatice Odabaş
Department of Medical Oncology, Haydarpasa Numune Training Research Hospital, University of Health Sciences, Istanbul 34785, Turkey
Berna Ömür Öksüzoğlu
Department of Medical Oncology, Ankara Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, 06200 Ankara, Turkey
Akif Doğan
Department of Medical Oncology, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, 34785 Istanbul, Turkey
Hande Nur Erölmez
Department of Medical Oncology, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, University of Health Sciences, 34785 Istanbul, Turkey
Mahmut Gümüş
Department of Medical Oncology, Istanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital, Istanbul 34890, Turkey
Background and Objectives: KRAS genes are among the most prominent oncogenes that trigger tumor formation in colorectal cancer (CRC) and serve as predictive biomarkers for resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. However, the prevalence and mutation spectrum of the KRAS gene family in mCRC patients in Turkey have not been sufficiently analyzed. This study investigates the frequency and distribution of mutations in the KRAS gene family across different regions of Turkey and examines gender-related variations. Materials and Methods: This multicenter observational study included 2458 histologically confirmed mCRC patients collected from 52 centers across Turkey. In a central laboratory, KRAS mutations in codons 12 and 13 were analyzed using polymerase chain reaction (PCR). Statistical analyses were performed using chi-square tests and Monte Carlo simulations, with a significance threshold set at p Results: Depending on the region, KRAS mutations were detected in 45% of patients, ranging from 39.6% to 47.5%. The mutation rate was significantly higher in female patients (48.8%) compared to male patients (42.6%) (p = 0.002). Codon 12 mutations were more frequent than codon 13 mutations. G12D, G12V, and G13D mutations accounted for 80% of all detected mutations. The G12V mutation was prevalent in female patients (p = 0.007). Based on region, mutation diversity was similar, and no statistically significant difference was found (p > 0.05). Conclusions: This large-scale, multicenter study provides the most comprehensive dataset of KRAS mutations in mCRC patients in Turkey. This study revealed regional trends, as well as gender differences. The findings highlight the importance of routine KRAS genotyping in guiding personalized treatment strategies, especially regarding candidate selection for anti-EGFR therapies. Further research is required to elucidate the prognostic and therapeutic implications of specific KRAS mutations.
