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.