Mutant-Enriched PCR and Allele-Specific Hybridization Reaction to Detect K-Ras Mutations in Stool DNA: High Prevalence in a Large Sample of Older Adults (Technical Briefs‪)‬

Given that somatic mutations of the K-ras gene are observed in ~40% of colorectal cancers (CRCs) (1-3) and in 80% of pancreatic cancers (4), mutant K-ras in stool specimens has been proposed as a potential component of marker combinations aimed at the early detection of these cancers (5-10). Conclusions drawn from existing studies must be viewed cautiously, however, because most of the study populations were highly selective and rather small (5-10), and different analytical techniques were used and may have led to different detection rates (5). For example, assays based on the amplification of DNA by mutant-enriched PCR are supposed to result in higher rates of K-ras-positive samples than other assays (11). Although higher detection rates may optimize sensitivity, another important question is whether specificity may be affected, i.e., whether diminutive amounts of mutant K-ras in stool can also be detected in average-risk people or, preferentially, in people with certain risk factors (e.g., as proposed for smokers) (12). To clarify these questions, which are highly relevant in regard to potential population-wide testing, large-scale investigations in the screening setting are needed. We investigated prevalence and potential determinants of mutant K-ras in stool (analyzed by mutant-enriched PCR and allele-specific hybridization reaction) in a large sample of unselected older adults and assessed the association with colonoscopic findings.