High frequency of NRAS mutations and RAS co-mutations in colorectal cancer from the Kurdistan region of Iraq: molecular and survival analysis

Mutations in RAS and PI3K pathway genes play a critical role in Colorectal Cancer (CRC) pathogenesis and therapy response, yet data from underrepresented populations remain limited. Molecular analysis was performed on 48 CRC cases from the Kurdistan region of Iraq to detect mutations in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146; exons 2–4), BRAF (codon 600; exon 15), PIK3CA (codons 542, 545, and 1047; exons 9 and 20), and AKT1 (codon 17; exon 4), and to correlate findings with histopathological characteristics and survival outcomes. NRAS mutations were the most frequently detected alterations (52.08%), followed by KRAS (47.92%) and PIK3CA (16.67%). A high frequency of co-mutations, particularly involving KRAS and NRAS, was observed, substantially exceeding frequencies reported in international cohorts; possible contributing factors including intratumoral heterogeneity and assay sensitivity are discussed. Tumor-associated inflammatory response and lymph node status demonstrated significant associations with patient survival. These findings from a small patient cohort suggest the need for further investigation of regional CRC molecular profiles using larger cohorts and orthogonal validation methods.