Detecting K-ras mutations in stool from fecal occult blood test cards in multiphasic screening for colorectal cancer.

ABSTRACT

Fecal occult blood testing (FOBT) is proven an efficient way of reducing mortality from colorectal cancer but has a relatively low positive predictive value (PPV). This study evaluated the ability to detect K-ras mutations in stool DNA from FOBT cards and to improve the PPV of the screening process. Two hundred and five consecutive positive FOBT cards and an arbitrary sample of 38 negative cards from a population-based screening program were included. K-ras mutations in FOBT card stool were sought using allele-specific hybridization. DNA was successfully amplified from 87.2% of cards. In 130 cases with positive FOBT and amplifiable DNA 23 malignancies and 25 adenomas were detected. In 34.8% of the malignancies, a mutation in K-ras was detected. The PPV for malignancies increased from 17.7% (all positive cards) to 60.0% if cards with four or more fields were positive and K-ras was positive (RR=2.66, 95% CI 1.2-6.1). Testing for K-ras mutations in DNA extracted from stool from positive FOBT cards is feasible. Sequential detection of cancer-associated genetic markers from FOBT-based stool samples may potentially help separate true from false positives in a FOBT-based screening process.