Kirsten Rat Sarcoma Viral Oncogene Homolog Mutations in Colorectal Cancer: Mutational Spectrum and Clinicopathological Associations from a Unicenter Study in Malaysia

Context: Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in colorectal cancer (CRC) and is essential for predicting response to anti-epidermal growth factor receptor-targeted therapy. However, contemporary data on the KRAS mutational spectrum and clinicopathological associations in Malaysian CRC patients remain limited. Aims: The present study aimed to determine the prevalence, mutational spectrum, and clinicopathological associations of KRAS mutations in Malaysian CRC patients undergoing routine molecular testing. Subjects and Methods: A retrospective unicenter study was conducted on 163 CRC patients diagnosed between 2013 and 2024 at Mahkota Medical Centre. KRAS mutation testing was performed on formalin-fixed paraffin-embedded tumor tissues using polymerase chain reaction-based sequencing targeting codons 12, 13, 59, 61, 117, and 146. Demographic and clinicopathological data were extracted from clinical records. Associations with KRAS mutation status were assessed using univariate analyses and multivariable logistic regression. Results: KRAS mutations were identified in 83 (50.9%) patients. Codon 12 mutations predominated (71.2%), with p.G12D as the most frequent variant (31.3%), followed by mutations in codons 13 (12.5%), 61 (11.3%), and 146 (5%). No mutations were detected in codons 59 or 117. Among patients with available staging data (71.8%), KRAS mutations were more frequently observed in advanced-stage disease; however, staging data were incomplete, particularly among KRAS wild-type patients. Multivariable analysis showed no statistically significant independent association between KRAS mutation status and clinicopathological variables. Conclusions: KRAS mutations are common among Malaysian CRC patients, with codon 12 variants predominating. Incomplete staging data and selection bias limit definitive conclusions regarding associations with disease stage.