Pathophysiology of Colorectal Cancer
How does colorectal cancer develop?
The pathogenesis of colon cancer is complex. Colon cancer results from the accumulation of multiple genetic alterations that happen in a specific sequence over a period of time. The genetic alterations may result from sporadic mutations or from mutations that are inherited as discussed under risk factors for rectal and colon cancer.
The APC gene, which has an essential role in the regulation of the growth of intestinal epithelial cells, and is frequently mutated resulting in FAP. APC mutations can lead to accumulation of a type of oncogene in the cells, which can promote cancer development.
The right-sided tumors usually grow as polypoid masses that bleed. The bleeding can often be in the form of occult bleeding. The right-sided tumors rarely cause obstruction, while the carcinomas of the left side (distal colon) usually lead to bowel obstruction due to constriction of the bowel as the lesions are generally annular shaped. The tumors of the distal colon may also present with bleeding.
Majority of colon cancers are left-sided, but of late there has been a steady increase in the incidence of right-sided colon cancer in the US, Europe and Asia. The anatomic shift probably results from response to carcinogens, increased longevity, or genetic factors with defects in mismatch repair genes.