The evolution of colorectal cancer genetics-Part 1: from discovery to practice.

Colorectal cancer (CRC) is an increasing burden on our society. Identifying those who are at the greatest risk and improving triage for treatment will have the greatest impact on healthcare. CRC is a prime paradigm for cancer genetics: the majority of disease results from stages of progression lending itself to prevention by early detection of the pre-disease (neoplastic) state. Approximately 10% represent well defined hereditary cancer syndromes. Hereditary CRC has the added benefit that many are slow growing and family members are armed with the knowledge of potential risk of associated carcinomas and empowerment to reduce the disease burden. This knowledge provides the indication for early endoscopic and/or surgical intervention for prevention or treatment of an entire family cohort. The molecular basis of CRC allows enhanced characterization of carcinomas, leading to targeted therapies.

The evolution of colorectal cancer genetics-Part 2: clinical implications and applications.

The genetic understanding of colorectal cancer (CRC) continues to grow, and it is now estimated that 10% of the population has a known hereditary CRC syndrome. This article will examine the evolving surgical and medical management of hereditary CRC syndromes, and the impact of tumor genetics on therapy. This review will focus on the most common hereditary CRC-prone diseases seen in clinical practice, which include Lynch syndrome (LS), familial adenomatous polyposis (FAP) & attenuated FAP (AFAP), MutYH-associated polyposis (MAP), and serrated polyposis syndrome (SPS). Each section will review the current recommendations in the evaluation and treatment of these syndromes, as well as review surgical management and operative planning. A highly detailed multigeneration cancer family history with verified genealogy and pathology documentation whenever possible, coupled with germline mutation testing when indicated, is critically important to management decisions. Although caring for patients with these syndromes remains complex, the application of this knowledge facilitates better treatment of both individuals and their affected family members for generations to come.