Genetic heterogeneity of colorectal cancer and the microbiome

Abstract

In 2020, the International Agency for Research on Cancer and the World Health Organization's GLOBOCAN database ranked colorectal cancer (CRC) as the third most common cancer in the world. Most cases of CRC (> 95%) are sporadic and develop from colorectal polyps that can progress to intramucosal carcinoma and CRC. Increasing evidence is accumulating that the gut microbiota can play a key role in the initiation and progression of CRC, as well as in the treatment of CRC, acting as an important metabolic and immunological regulator. Factors that may determine the microbiota role in CRC carcinogenesis include inflammation, changes in intestinal stem cell function, impact of bacterial metabolites on gut mucosa, accumulation of genetic mutations and other factors. In this review, I discuss the major mechanisms of the development of sporadic CRC, provide detailed characteristics of the bacteria that are most often associated with CRC, and analyze the role of the microbiome and microbial metabolites in inflammation initiation, activation of proliferative activity in intestinal epithelial and stem cells, and the development of genetic and epigenetic changes in CRC. I consider long-term studies in this direction to be very important, as they open up new opportunities for the treatment and prevention of CRC.

Keywords: Bacterial metabolites; Colorectal cancer; Colorectal polyp; Epigenetic changes; Gut microbiota; Stem cells.