Genetic Testing Use and Expectations in Early Onset Colorectal Cancer

A substantial proportion of colorectal cancer (CRC) diagnosed under age 50, or early-onset colorectal cancer (EOCRC), is associated with a hereditary cancer syndrome. It is of utmost importance to identify these patients to customize cancer treatment options, decrease the risk of metachronous cancers, and facilitate testing within the family to identify carriers. The purpose of this paper is to review the evolution of genetic evaluation in patients with EOCRC, review current best practices, and describe areas ripe for future work and research. Fourteen to 25% of all EOCRCs are associated with a pathogenic germline variant. These variants are found in genes typically associated with EOCRC, such as Lynch syndrome or biallelic MUTYH, as well as genes that are not necessarily congruent with EOCRC phenotypes such as polyposis syndromes or hereditary breast and ovarian cancer syndromes. Professional societies now recommend comprehensive multigene panel testing in all patients with EOCRC, regardless of personal history, family history, or tumor characteristics.