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Jonathan Potack and Steven H. Itzkowitz

The rationale for screening for colorectal cancer (CRC) is well established, and several tests are currently recommended. Colonoscopy has become a popular modality in most of the United States and other countries. Despite colonoscopy being highly accurate and therapeutic, many patients prefer a noninvasive screening test. Testing stool for occult blood by the chemical guaiac reagent (gFOBT) has been available for decades and is effective at reducing mortality from CRC. However, because of limitations in sensitivity and specificity, newer fecal immunochemical tests (FITs) were developed that detect occult blood using enzyme immunoassays. Because of their improved sensitivity and specificity, FITs have replaced gFOBT for screening in many settings. Detecting neoplasia-associated genetic changes in stool has also become feasible; first-generation stool DNA tests showed greater sensitivity for CRC, with similar specificity to gFOBT. Improvements to stool DNA tests have made them more sensitive and less complex. As the performance characteristics for FIT and stool DNA tests continue to evolve, stool-based testing for CRC is expected to become a more reliable component in the armamentarium for CRC screening.

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Jeremy Matloff, Aimee Lucas, Alexandros D. Polydorides, and Steven H. Itzkowitz

Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, and accounts for 2% to 3% of all colorectal cancers. These tumors are caused by germline mutations of DNA mismatch repair genes, which result in microsatellite instability. Colonic and extracolonic malignancies can occur at a young age, and are often diagnosed at a late stage because of underrecognition of the syndrome. Identifying individuals with LS before the development of these malignancies decreases mortality because of frequent screening and surveillance of colonic and extracolonic cancers. Moreover, family members of these individuals can be tested and begin screening at a young age if appropriate. Classically, Amsterdam criteria and Bethesda guidelines have been used to identify at-risk individuals; however, these tools miss a significant number of cases. As the molecular basis for LS has been clarified, more sophisticated strategies have emerged. Testing all colorectal cancers for loss of mismatch repair proteins, known as universal screening, is a strategy used to identify individuals at risk for LS. This approach has been shown to be more sensitive than previous methods that rely on family history. Implementation of universal tumor testing necessitates a systematic approach to positive results in order to have maximal effect, and could prove to be the most cost-effective approach to reducing cancer mortality in patients with LS.