Quantitation of DNA from exfoliated colonocytes isolated from human stool surface as a novel noninvasive screening test for colorectal cancer.
The only widely used screening test for early detection of colorectal cancer, the fecal occult blood test, lacks both sensitivity and specificity because it relies upon incidental bleeding rather than the neoplastic process. With the purpose of developing a new noninvasive diagnostic approach, we quantified DNA extracted from cells isolated from the surface of human stools by a novel procedure. Stools collected from 28 healthy individuals, 17 colorectal cancer patients, and 11 colorectal polyp patients were analyzed. A stool DNA index (SDNAI), expressed as DNA amount in nanograms per gram of stool, had a remarkable 4.5-fold difference in mean values between colorectal cancer patients and healthy people of comparable age. SDNAI was 2133 +/- 407 in the cancer group versus 469 +/- 65 in healthy people of the older (> 50 years) age group (P = 0.0005). The difference was independent of tumor location and size. If 700 ng of DNA/g of stool was taken as a cutoff SDNAI value in discrimination between older healthy people and cancer patients, sensitivity and specificity values reached 1.00 and 0.81, respectively. Age dependence of SDNAI was demonstrated by substantially lower SDNAI values (mean, 227 +/- 41) in younger healthy individuals. Polyp patients sometimes displayed elevated SDNAI values, but considerable variation was observed (mean, 1215 +/- 548). These preliminary findings indicate that SDNAI provides a novel, simple, and powerful noninvasive test for colorectal cancer early detection and screening. The fundamental advantage of the SDNAI is that it directly characterizes colonic epithelium involved in carcinogenesis.
Loktionov
A
A
Dunn Clinical Nutrition Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
O'Neill
I K
IK
Silvester
K R
KR
Cummings
J H
JH
Middleton
S J
SJ
Miller
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003111:Colonic Polyps / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis* / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D008875:Middle Aged
D004273:DNA, Neoplasm