Incremental advances in excremental cancer detection tests.

Colorectal cancer is often considered the most preventable, yet least prevented, cancer. What makes it so preventable is the existence of a precancerous phase of the disease, the adenomatous polyp, which has a rather long dwell time and is usually readily detectable by structural examinations of the colon, such as colonos-copy, sigmoidoscopy, and more recently, computed tomography colonography. Indeed, the removal of adenomas markedly reduces the subsequent development of colorectal cancer. Thus, screening for colorectal cancer, which has been endorsed by all major medical societies, received a grade A recommendation by the United States Preventive Services Task Force in its most recent guidelines (1). Over the last decade, colonoscopy has become the preferred screening test in the United States because it not only detects cancers and polyps with high accuracy but is also therapeutic by virtue of its ability to remove polyps and even early cancers. Despite its considerable strengths, colonoscopy is still associated with organizational, logistical, and patient-related barriers that limit its full acceptance as a screening method. For this reason , stool-based screening tests are an attractive alternative for many screen-eligible people because the tests are noninvasive, can be done in the privacy of the home, and do not require a cleansing bowel preparation or the need to miss work. Moreover, in parts of the world where colonoscopy resources are limited, stool-based tests, which to date have been based on detecting occult blood, remain the cornerstone of colorectal cancer screening. Indeed, for decades, stool-based tests relied on detecting occult blood with the chemical guaiac reagent (eg, Hemoccult). Whereas this approach reduces colorectal cancer mortality by one-third when the test is performed annually, guaiac-based tests, including the more sensitive versions (eg, Hemoccult SENSA), have limited sensitivity and specifi city for colorectal cancer, are quite poor at detecting adenomas, and rely on patients complying with annual, if not biennial, testing to demonstrate effi cacy. Newer fecal immunochemical tests have better sensitivity and specifi city than guaiac fecal occult blood tests, but blood is a rather nonspecifi c screening target, with the potential for false positives and false negatives. Because so much is known about the molecular pathogenesis of gastrointestinal neoplasia, DNA is becoming a more relevant and promising analyte in stool. In the last decade, the feasibility of detecting mutant human-derived DNA among the morass of bacterial DNA in stool became a reality. This soon led to the development of …