THE ROLE OF THE MOLECULAR-BIOLOGICAL MARKER CDKN2AIN THE EARLY DIAGNOSIS OF COLORECTAL CANCER

Relevance: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, largely due to late diagnosis. In recent years, particular importance has been given to the search for accessible and sensitive molecular markers for the early detection of precancerous changes, especially in resource-limited countries, including Uzbekistan, where national screening programs are absent and access to colonoscopy remains limited. One of the most studied markers is hypermethylation of the tumor suppressor gene CDKN2A, which plays a key role in cell cycle regulation. The study aimed to investigate the frequency of CDKN2A promoter hypermethylation in patients with colonic and rectal polyps and polyposis, as well as its association with morphological features of dysplasia.Methods: The study included 31 patients with precancerous intestinal lesions. Mucosal biopsies and blood plasma samples were analyzed using methylation-specific PCR (MSP-PCR).Results: CDKN2A hypermethylation was detected in 17 patients (54.8%). The methylation frequency was 65% in patients with polyps and 36.4% in those with polyposis (p=0.043). A direct association with morphological changes was established: patients with hypermethylation more frequently exhibited moderate dysplasia (70.6%), whereas in marker-negative cases mild dysplasia or its absence predominated.Conclusion: The findings confirm that CDKN2A hypermethylation is an early marker in the pathogenesis of CRC, closely associated with the progression of precancerous lesions. The MSP-PCR method demonstrated high sensitivity and accessibility, making it a promising tool for implementation in regional laboratories of Uzbekistan. CDKN2A may serve as a risk stratification criterion, a component of molecular screening, and a basis for personalized surveillance of patients with precancerous intestinal changes.