Clinical meaning
Colorectal cancer (CRC) develops through the adenoma-carcinoma sequence over 10-15 years. Normal colonic epithelium acquires mutations in APC (tumor suppressor, initiating adenoma formation), KRAS (oncogene, promoting growth), SMAD4/DCC (progression), and TP53 (malignant transformation). The serrated neoplasia pathway involves BRAF mutation and CpG island methylation. Screening is effective because: 1) the disease has a long preclinical detectable phase, 2) removal of precancerous adenomas prevents cancer development, and 3) early-stage CRC has excellent survival (90% 5-year survival for stage I vs 14% for stage IV). CRC is the second leading cause of cancer death in the US; screening has reduced mortality by 50-60% in screened populations.
Diagnosis & workup
Diagnostics & workup: - Colonoscopy: gold standard; visualizes entire colon; allows biopsy and polypectomy; every 10 years if normal; repeat based on polyp findings (1-2 small tubular adenomas → 7-10 years; 3-10 adenomas or >10mm or villous/HGD → 3 years) - Stool-based tests: FIT (fecal immunochemical test) annually; FIT-DNA (Cologuard) every 3 years -- positive results require colonoscopy for confirmation - Flexible sigmoidoscopy: every 5 years (only examines rectum and distal colon; misses proximal lesions) - CT colonography (virtual colonoscopy): every 5 years; non-invasive but requires bowel prep; polyps >6mm require follow-up colonoscopy - Screening guidelines: USPSTF recommends screening ages 45-75 (Grade B for 45-49, Grade A for 50-75); ages 76-85 selective screening based on individual risk