Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Approximately 65% of all CRC cases are sporadic, and may be associated with environmental factors or polygenic in inheritance from multiple low-penetrance susceptibility genes and do not exhibit familial clustering of cancer.
Nearly 30% of CRC cases arise from moderately penetrant, inherited susceptibility genes, possibly interacting with environmental factors.1,2 In families with moderately penetrant, inherited susceptibility genes there is a clustering of CRC cases in excess of that expected by chance.3 Studies have shown that the risk for CRC is 2- to 3-fold higher than expected in the general population if a first-degree relative is diagnosed with CRC. This risk increases to 3-fold or higher if 2 first-degree relatives have CRC or a single first-degree relative is diagnosed with CRC prior to 50 years of age. An individual's risk for developing CRC is also increased if a second- or third-degree relative has CRC or a first-degree relative has a colorectal adenoma.4,5
Among CRC cases, 3% to 5% are caused by highly penetrant inherited syndromes, including Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), MYH-associated polyposis (MAP), and rare hamartomatous polyposis syndromes. This article focuses on the diagnostic features, evaluation, and management of Lynch syndrome, and includes a brief discussion of other inherited CRC syndromes.
Dr. Grover has disclosed that she receives research funding from the National Cancer Institute Grant Number R25 CA 092203. Dr. Syngal has disclosed that she receives research support funding from the National Cancer Institute, is a consultant for Interquest Inc., and is an advisor for Archimedes, Inc.
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