Inherited colorectal cancer syndromes

Abstract

Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events, but up to 5% are attributed to known monogenic disorders including Lynch syndrome, familial adenomatous polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers, and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer.

FIGURE 1

Evaluation for genetic predisposition in patients with nonpolyposis CRC. MSI indicates microsatellite instability; MSS, microsatellite stable. ^§PREMM_1,2,6 score can be calculated at the following Web site: www.dfci.org/premm; other models (MMRpro, MMRpredict) may also be used with their own specified cutoff scores. *Consider BRAF or MLH1 hypermethylation testing. **Surveillance recommendations based on personal and family history.

FIGURE 2

Evaluation for genetic predisposition in patients with CRC and/or polyps. *Patients with 10 or more adenomas should be closely followed up with annual colonoscopy, and genetic testing may be considered based on personal/family history.