Colorectal cancer. From genetics to prevention

The adenoma carcinoma sequence postulates that colorectal carcinomas arise from precursor lesions, called adenomas. All adenomas contain dysplastic epithelium that arises from mutations in either the adenomatous polyposis coli gene or DNA mismatch repair genes. The earliest lesion detected with dysplasia is the aberrant crypt focus.

Over time, as this lesion acquires additional mutations, it evolves into a classic adenomatous polyp. Adenomatous polyps are classified as tubular, tubulovillous, or villous. Generally, as polyps increase in size, the degree of dysplasia worsens, the villous component increases, the number of genetic abnormalities increases, and the likelihood of harboring invasive carcinoma increases.

Carcinomas associated with DNA mismatch repair mutations are more likely to be poorly differentiated and incite a host lymphocytic response. These tumors seem to have a better prognosis, stage for stage, than typical colorectal carcinomas.

Evidence suggests that subtypes of serrated polyps, particularly TSA and SSA/P, can lead to adenocarcinoma through the serrated pathway. Moreover, the data indicate that the SSA/P are the precursors of colorectal carcinoma by MSI and may be subject to rapid progression to malignancy. An important step to reduce the incidence of CRC initiated by the serrated pathway is to improve the detection of serrated polyps and to ensure their complete removal during endoscopy.

Understanding of the so called serrated carcinogenesis pathway is an important step forward in expanding possibilities in the prevention of CRC.