Stool DNA Testing and Colon Cancer Prevention: Another Step Forward
Despite the recognition that colon cancer is largely preventable, it remains the second leading cause of cancer-related deaths in the United States. Historically, screening approaches have sought to detect established cancer, but the identification of precancerous adenomatous polyps is clearly the preferable goal. Not all adenomas progress to cancer, but those that are larger than 1 cm or contain villous histology or high-grade dysplasia are most likely to do so. The current multisociety guidelines now emphasize detection of precancerous polyps as the most effective strategy to prevent deaths from colon cancer, and structural examinations, such as colonoscopy, are recommended for this purpose (1). Testing for occult blood in stool is notoriously insensitive for detecting adenomas (2).
The adenoma-to-carcinoma sequence in colon cancer is based on the stepwise accumulation of specific genetic alterations that parallel the histopathologic progression from preneoplasia to neoplasia (3). Researchers have cleverly translated these insights into molecular diagnostic assays that detect gene mutations in tumor cells sloughed into stool. In 1992, the first report of K-ras mutations in the stool of patients with colon cancer ushered in the era of stool DNA testing (4). Since then, advances in the specific genes analyzed, techniques to separate and preserve tumor DNA from the vast quantities of bacterial DNA, and …
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