Abstract
Colorectal cancer (CRC) emerged due to genetic mutations that fuel tumor development and influence patient outcomes. This research investigates KRAS, BRAF, and PIK3CA mutations in Iraqi Kurdish patients to assess their biological relevance and impact on clinical outcomes. Clinical and pathological data were collected from 150 patients' medical profiles. DNA was extracted from FFPE samples for KRAS, BRAF, and PIK3CA mutation analysis. Variations in KRAS and BRAF 600/601 were identified by polymerase chain reaction (PCR) amplification followed by hybridization assays. Real-time PCR was utilized to detect PIK3CA mutations. Tumors were predominantly located in the colon (80%) and classified as adenocarcinomas (88%), with stage III being the most frequent (36%). Metastases were observed in 72.67% of cases, primarily in the liver (46.67%). KRAS mutations were identified in 37.33% of cases (mainly in codons 12 and 13), while BRAF V600E mutations occurred in 10.67%, and PIK3CA mutations were detected in 18.67%, with exon 9 alterations more common than those in exon 20. KRAS mutations were strongly associated with liver metastases (p=0.006), and BRAF mutations correlated with peritoneal metastases (p=0.0001). Co-mutations of KRAS and PIK3CA appeared in 7.33% of cases, while BRAF and PIK3CA co-mutations were rarer (1.3%). Our study underscores the complexity of CRC and the pivotal role of KRAS, BRAF, and PIK3CA variations in tumor progression and outcomes in Iraq's Kurdistan Region, highlighting the importance of molecular profiling in clinical care.