KRAS gene mutation status in colorectal cancer in the Republic of Kazakhstan: Results of the first multicentre retrospective study

Colorectal cancer ranks third worldwide in terms of the number of new cases and second in terms of cancer-related mortality. KRAS gene status determines the eligibility for anti-EGFR therapy; however, prior to this study, data on Kazakh patients had only been collected in individual clinics and had not been collated. The aim was to determine the frequency and spectrum of KRAS mutations in patients with verified colorectal cancer across several oncology centres in Kazakhstan and to assess their association with clinical and epidemiological parameters. This retrospective, multicentre study included 332 patients with morphologically confirmed stage II-IV colorectal cancer. Mutation status was determined using real-time allele-specific polymerase chain reaction on FFPE tissue blocks. The Pearson’s χ² test (Fisher’s exact test for small expected frequencies) was used to compare groups; the strength of association was assessed using the odds ratio with a 95% confidence interval; logistic regression was applied for multivariate analysis. A KRAS mutation was detected in 149 patients (44.9 ± 2.7%), whilst the wild-type was found in 183 (55.1 ± 2.7%). The majority of mutations (80.5%) occurred at codon 12, with the most common variants being G12D (32.2%), G12V (24.8%) and G13D (19.5%). No statistically significant association was found between mutation status and gender (p = 0.46), ethnicity (p = 0.30), age (p = 0.29) or tumour site (p = 0.45-0.74 depending on the grouping); in the multivariate model, none of these factors proved to be an independent predictor. The frequency of KRAS mutations in the Kazakh cohort (44.9%) falls within the global range of 40-45%, and the pattern of variants mirrors the findings of major international studies. The results confirm the need for routine extended RAS testing in cancer centres in Kazakhstan