Genesis of colon cancer and significance for diagnosis and prognosis

Kolorektalni karcinom (CRC) jedan je od najčešćih zloćudnih bolesti i globalni svjetski problem. Zajednički cilj je smanjiti pojavnost ove bolesti zbog čega su prevencija i rano otkrivanje od iznimne važnosti. Bolest se definira kao maligni tumor epitelnih stanica sluznice kolona, a nastaje uslijed interakcija stečenih i nasljednih genetskih promjena s vanjskim čimbenicima tijekom duljega vremenskoga perioda. Glavni mehanizmi nastanka uključuju kromosomsku nestabilnost (CIN), mikrosatelitnu nestabilnost (MSI) te hipermetilaciju CpG otoka (CIMP). Nakupljaju se mutacije u onkogenima (KRAS, BRAF), tumorskim supresorskim genima (APC, TP53), nastaju delecije kromosoma (18q), disfunkcija telomera. Događaju se promjene u ekspresiji gena koji kodiraju za mitotičke kinaze (PLK-1, AURK) te je promijenjena regulacija stanične signalizacije i diferencijacije (APC/Wnt signalni put, Ras-Raf- MAP-kinazni put). Učestalost od smrtnosti još uvijek je u porastu zbog čega se istražuje genetska podloge bolesti i otkrivaju novi molekulski biljezi kako bi se olakšala dijagnostika i liječenje. Prioritet je otkrivanje karcinoma u što ranijoj fazi pronalaženjem novih minimalno invazivnih biljega kako bi se povećala stopa preživljavanja pacijenta.Colorectal cancer (CRC) is one of the most common malignancies and a global problem. The common goal is to reduce the incidence of these disease, which is why prevention and early detection are extremely important. Disease is defined as a malignant tumor of the epithelial cells of the colonic mucosa, and occurs due to the interaction of acquired and inherited genetic changes with environmental factors over a long period of time. The main mechanisms of formation include chromosomal instability (CIN), microsatellite instability (MSI) and hypermethylation of CpG islands (CIMP). Mutations accumulate in oncogenes (KRAS, BRAF), tumor suppressor genes (APC, TP53), occurs chromosome deletions (18q), telomere dysfunction. Changes in the expression of genes encoding mitotic kinases (PLK-1, AURK) occur and the regulation of cell signaling and differentiation (APC/Wnt signaling pathway, Ras-Raf-MAP-kinase pathway) is altered. The incidence of death is still increasing which is why the genetic underpinnings of the disease are being investigated and new molecular biomarkers are being discovered to facilitate diagnosis and treatment. The priority is to detect cancer at the earliest possible stage, with finding new minimally invasive biomarkers to increase the patient's survival rate