RAS somatic variants are predictors of resistance to anti-EGFR therapy for colorectal cancer (CRC) and affect the outcome of the disease. Our study aimed to evaluate the frequency of RAS, with a focus on KRAS variants, and their association with tumor location and some clinicopathological characteristics in Bulgarian CRC patients. We prospectively investigated 236 patients with advanced and metastatic CRC. Genomic DNA was extracted from FFPE tumor tissue samples, and commercially available kits were used to detect RAS gene somatic mutations via real-time PCR. A total of 115 (48.73%) patients tested positive for RAS mutations, with 106 (44.92%) testing positive for KRAS mutations. The most common mutation in exon 2 was c.35G>T p.Gly12Val (32.56%). We did not find a significant difference in KRAS mutation frequency according to tumor location. However, patients with a mutation in exon 4 of KRAS were 3.23 times more likely to have a tumor in the rectum than in other locations (95% CI: 1.19-8.72, p = 0.021). Studying the link between tumor location and KRAS mutations in exon 4 is crucial for better characterizing CRC patients. Further research with larger cohorts, especially in rectal cancer patients, could provide valuable insights for patient follow-up and treatment selection.
Keywords: KRAS; RAS; colorectal cancer; left-sided colon cancer; right-sided colon cancer.