MUTANT K-RAS IN APPARENTLY NORMAL MUCOSA OF COLORECTAL-CANCER PATIENTS - ITS POTENTIAL AS A BIOMARKER OF COLORECTAL TUMORIGENESIS

Background. The best way to reduce the incidence of colorectal cancer mortality would be to prevent this cancer. However, none of the biomar kers proposed can accurately identify persons at increased risk of col orectal cancer or those at low risk. As a possible genetic biomarker, K-ras mutations, which are frequently found in colorectal cancers, wer e analyzed in apparently normal colorectal mucosa. Methods. Nonneoplas tic mucosa and tumor tissues were collected at surgery from 70 patient s with colorectal cancer: one sample each from 50 patients (group A) a nd multiple samples from the other 20 patients (group B). Mutant K-ras codon 12 was analyzed by the enriched polymerase chain reaction (EPCR ), by which one mutant can be detected among 10(3) to 10(4) normal all eles. Results. Only with the aid of EPCR was mutant K-ras detected in nonneoplastic mucosa of nine patients (18%) in Group A and five patien ts (25%) in Group B. This increased incidence could be attributed to t he multiple tissue sampling. The presence of mutant K-ras in nonneopla stic mucosae was not consistently correlated with that in the tumors. These findings suggest that the mutant Kras identified in nonneoplasti c mucosa actually represents de novo mutations, which may be initiated by different etiologic factors and at different times. Conclusion. Mu tant K-ras detected in apparently normal mucosa should be a useful bio marker for identifying persons at higher risk of colorectal cancer. Ou r study also emphasizes the need for improving the method for sample c ollection to achieve true representation of the colorectal mucosa.