Identification of subjects at risk for colorectal carcinoma through a test based on K-ras determination in the stool.
OBJECTIVE
The gold standard for screening for colorectal carcinoma is colonoscopy. The aim of this study was to compare endoscopic results with those obtained using the noninvasive screening test of K-ras determination in the stool in a large population of patients undergoing colonoscopy.


METHODS
Two hundred thirty consecutive patients were studied by K-ras amplification on stool-derived DNA using polymerase chain reaction and oligomer-specific hybridization.


RESULTS
Wild-type K-ras was amplified in 103 of 230 patients (44.8%), the rate of amplification being directly proportional to the presence of an organic disease of the intestine characterized by hyperproliferating mucosa. In 30 of these 103 patients (29.1%), a K-ras mutation was found. Four of 5 with early colorectal carcinoma, all who had K-ras mutations in the tumor, were identified. In first-degree relatives of patients with colorectal carcinoma, all subjects either carrying adenomas > 1 cm in diameter or multiple smaller adenomas were identified. In patients with inflammatory bowel disease, the test identified the only patient with neoplastic transformation.


CONCLUSIONS
The sensitivity and specificity of K-ras determination on stool-derived DNA in patients with colorectal carcinoma, in first-degree relatives of patients with colorectal carcinoma, and in patients with inflammatory bowel disease support the opportunity of a large-scale trial to validate its use as a screening test.
Villa
E
E
Department of Internal Medicine, University of Modena, Italy. Ericavil@unimail
Dugani
A
A
Rebecchi
A M
AM
Vignoli
A
A
Grottola
A
A
Buttafoco
P
P
Losi
L
L
Perini
M
M
Trande
P
P
Merighi
A
A
Lerose
R
R
Manenti
F
F
D000236:Adenoma / Q000235:genetics / Q000517:prevention & control; D000328:Adult; D000368:Aged; D001483:Base Sequence; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000517:prevention & control; D004252:DNA Mutational Analysis; D005243:Feces / Q000737:chemistry*; D005260:Female; D005784:Gene Amplification; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity