Patients with a family history of CRC account for up to 30% of all cases. Those with a first-degree relative with a history of CRC have 2- to 4-times the risk of developing the disease, depending on the age at diagnosis and the number of affected relatives.

Hereditary syndromes account for about 5% of cases. The most common of these is Lynch syndrome, which accounts for about 2% to 4% of cases. This syndrome is associated with mutations in genes associated with the DNA mismatch repair system.

The second most common predisposing genetic syndrome is familial adenomatous polyposis (FAP), which accounts for less than 1% of cases. This syndrome is associated with mutations in the APC tumor-suppressor gene. Other familial syndromes, such as hamartomatous polyposis syndromes are very rare.