Colorectal Cancer Basics

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer death in North America. Over 90% of CRCs are adenocarcinomas arising from the glandular epithelial cells lining the colonic mucosa. Understanding the adenoma-carcinoma sequence is fundamental: most CRCs develop from pre-existing adenomatous polyps through a stepwise accumulation of genetic mutations over 10-15 years. The adenoma-carcinoma pathway begins with normal colonic epithelium acquiring a mutation in the APC (adenomatous polyposis coli) tumour suppressor gene, leading to dysregulated cell proliferation and formation of an adenomatous polyp. Subsequent mutations in KRAS oncogene, SMAD4, and TP53 tumour suppressor gene drive progression from small adenoma to advanced adenoma to invasive carcinoma. This sequence typically takes 10-15 years, providing a critical window for screening and early intervention through polyp removal (polypectomy). An alternative pathway, the serrated polyp pathway, accounts for 20-30% of CRCs and involves serrated polyps rather than conventional adenomas. These cancers are more common in the right (proximal) colon and are associated with BRAF mutations, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI). They can be more...