Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults.
BACKGROUND
Testing for mutant K-ras in stool has been proposed for the detection of pancreatic and colorectal cancer (CRC). Different analytical techniques have been developed, but studies of this biomarker in the general population are lacking. We investigated the prevalence and potential determinants of mutant K-ras in stool in a large sample of unselected older adults and assessed the association with colonoscopic findings.


METHODS
In stool samples from 875 older adults (age range 50-75 years) participating in a large-scale population-based cohort study, we used mutant-enriched PCR and allele-specific hybridization reaction to analyze mutations in codons 12 and 13 of the K-ras gene. We assessed the association between mutant K-ras in stool and risk factors for gastrointestinal cancer sites, exocrine pancreatic insufficiency determined by fecal pancreas elastase 1, and colonoscopic findings.


RESULTS
The overall prevalence of mutant K-ras in stool was 8% (95% confidence interval 6%-10%). There was a tentative association between increased fecal pancreas elastase 1 and mutant K-ras in stool (P = 0.09). Patients with advanced colorectal neoplasia diagnosed within 2 years after stool collection (24 with advanced adenomas, 7 with CRC) all tested negative.


CONCLUSIONS
The proposed assay identifies mutant K-ras in stool at a higher prevalence than has been reported for other analytical techniques. Our findings do not support the use of this assay for CRC screening, but its potential use for early detection of pancreatic cancer (in combination with other markers) requires further investigation.
Haug
Ulrike
U
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. u.haug@dkfz.de
Hillebrand
Timo
T
Bendzko
Peter
P
Löw
Michael
M
Rothenbacher
Dietrich
D
Stegmaier
Christa
C
Brenner
Hermann
H
D000236:Adenoma / Q000175:diagnosis / Q000235:genetics; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics; D004247:DNA / Q000032:analysis*; D005243:Feces / Q000737:chemistry*; D005260:Female; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010196:Pancreatic Elastase / Q000032:analysis; D016133:Polymerase Chain Reaction; D012306:Risk
D004247:DNA; D010196:Pancreatic Elastase