Amoebiasis primarily affects the colon because the causative organism, *Entamoeba histolytica*, invades the colonic mucosa after ingestion of contaminated food or water. This leads to ulceration and inflammation of the colonic lining, causing symptoms such as bloody diarrhea and abdominal pain. Although the liver can be secondarily involved via hematogenous spread (amebic liver abscess), the initial and primary site of infection is the colon. Effective treatment targets this region to prevent complications.

Reference: Harrison's Principles of Internal Medicine, Jameson et al., 20th Edition.