تست ژنتیک و سرطان روده زودرس Genetic Testing and Early Onset Colon Cancer

Although there have been encouraging decreases in the overall incidence of colorectal cancer (CRC) in the United States, a discouraging rise in incidence among those under 50 years has emerged.1 This increase has ranged from 1.0% to 2.4% annually, and curiously, most of these early onset cases have been localized to the distal colon and rectum. The precise etiologic factors underlying this trend have yet to be elucidated. Genetic risk factors can predispose to early onset colon cancer, and recognizing these hereditary colon cancer syndromes is critical to the management of affected individuals and their family members. Since the cloning of the APC gene that underlies the familial adenomatous polyposis syndrome in 1991, there has been an explosion in the number of genes (now >20) linked to hereditary colon cancer risk.2 The best understood are the high-penetrance genes associated with the classic Mendelian syndromes: Lynch and familial adenomatous polyposis. Many other genes that exhibit moderate penetrance are not as well-understood, and the associated cancer risks remain incompletely defined. On a practical level, most known genes associated with increased CRC risk are now captured on gene “panel” tests, although even more comprehensive panels that include genes associated with all cancer types are also available. Stoffel et al3 sought to define the frequency of germline genetic alterations in patients diagnosed with CRC <50 years of age by retrospectively reviewing genetic test results at a large academic center. There were 430 individuals who attended a genetics clinic, and 315 underwent routine testing as clinically indicated. The testing strategies included syndrome-specific testing and/or panel testing, and 117 individuals participated in more comprehensive researchbased testing. In aggregate, a germline mutation was identified in 20% of patients (85 of 430). Most mutations were associated with the high-penetrance syndromes: Lynch syndrome (58 of 85 [68%]) and familial adenomatous polyposis/MYH-associated polyposis (20 of 85 [24%]).