Can we identify the high-risk patients to be screened? A genetic approach.

Our understanding of the mechanisms that lead to colorectal cancer expands each year. Patients with a genetic predisposition to colorectal cancer have significantly increased risks for developing this malignancy over their lifetime. These risks can approach an 80 to nearly 100% likelihood of colorectal malignancy with some of the known cancer predisposition syndromes [Burt and Neklason: Gastroenterology 2005;128:1696-1716 and Rowley: Annu Rev Med 2005;56:539-554]. Although these inherited syndromes have a genetic basis, affected individuals are often initially seen by medical professionals outside the genetics realm. Gastroenterologists in particular have a key role in identifying patients at high risk for an inherited colorectal cancer predisposition syndrome and referring them on for directed genetics evaluation. In this review, we will focus on the presenting features and recommended screening and treatment protocols for six syndromes that predispose to colorectal carcinoma. The underlying genetic basis of each syndrome will be discussed, as well as specific guidelines for patient identification. Familial adenomatous polyposis will be covered first, followed by Lynch syndrome, attenuated familial adenomatous polyposis, MYH-associated polyposis, hereditary mixed polyposis, and hyperplastic polyposis. Other rare syndromes (the hamartomatous polyposis syndromes) will be summarized in table form. Finally, we will give some general guidelines for when to first suspect colorectal cancer syndromes, a summary of family history taking techniques that can be used in the primary care setting and a review of the referral, genetics appointment and postgenetics consultation process. Through this review, we hope to show that the identification of high-risk patients is possible, though sometimes difficult.