Background Few studies have addressed the prevalence and prognostic impacts of KRAS mutations in Saudi patients with colorectal cancer (CRC). The present study aimed to address the prevalence of KRAS mutations and evaluate their impact on clinical outcomes (if any) among Saudi patients. Methods This retrospective cohort study was conducted at King Saud University Medical Centre (KSUMC), Saudi Arabia. All medical records of biopsy-proven CRC patients between 2015 and 2021 were reviewed. Statistical analysis was carried out to address the associations between KRAS mutations and the clinicopathological patients' variables and survival. Results KRAS mutations were found in 97/194 (50%) CRC patients. In comparison to wild type KRAS tumors, KRAS- mutated ones had shown a trend toward right-sided tumors (30% and 4.3% vs 16% and 1.1%, p-value = 0.032, respectively) and peritoneal metastases (34% vs 19%, p-value = 0.014). Older age at diagnosis, gender, tumor grade, microsatellite instability (MSI), tumor stage (T), and the presence of distant metastasis were independent prognostic factors for poor overall survival (OS). There was no significant association between KRAS mutations and the hazard of mortality (HR: 0.653, 95% CI 0.873-1.134, p = 0.131). For progression-free survival (PFS), older age at presentation, MSI, tumor nodal stage (N), the presence of liver and lung metastasis, and recurrence were poor prognostic factors for PFS. There was no significant relation between KRAS mutations and PFS (HR ratio: 0.756, 95% CI 0.229-2.497, p = 0.646). Conclusions The prevalence of KRAS mutations in CRC patients was similar to that observed in previous studies of Saudi patients. KRAS mutations showed a trend toward right-sided tumors and peritoneal metastases. Survival was significantly related to different clinicopathologic variables of the study cohort but was not affected by the KRAS mutational status.

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