Colorectal cancer is one of the most common
malignancies in the western world. About 60,000 Americans die of
colorectal cancer each year. The annual incidence rate in Israel is 40 per 100,000 persons, namely a total of 2,000 new cases each year. An important step in the progression of
colorectal cancer includes induction of activating mutations in the proto-oncogene K-ras. The mutations in K-ras appear early during
tumorigenesis, at the intermediate
adenoma stage, and thus can be used as a
biomarker for early detection in about 40% of colonic
tumors. A large yet unknown number of mutated cells are shed from the developing
tumor during its progression. Indeed, K-ras mutations were detected in
DNA isolated from stool obtained from symptomatic and asymptomatic patients with
colorectal cancer, suggesting a novel approach for a noninvasive screening procedure. However, severe difficulties in obtaining reproducible yields of amplifiable
DNA from stool, and usage of nonquantitative, time-consuming procedures, hampered further progress in the utilization of K-ras mutations for the early detection of
colorectal cancer. Apparently a novel protocol is required that provides reproducible output of amplifiable
DNA from small amounts of stool, detects if K-ras mutated
DNA is present, and determines the quantity of K-ras mutated cells in the stool sample. In addition, this protocol should be simple, robotics compatible, and thus suitable for cost-effective, large-scale mutation screening. Molecular assays for detecting K-ras mutations and additional
biomarkers in stool
DNA promise to be highly sensitive, specific, and cost-effective. As such they should be very effective when used in
chemoprevention studies and screening protocols for
colorectal cancer.