Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.
BACKGROUND
DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues.


OBJECTIVE
The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia).


RESULTS
We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%.


CONCLUSIONS
NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals.


BACKGROUND
DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating characteristics; AUROC = area under the receiver operating characteristics curve.
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
E M
EM
Ionescu
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
T
T
Nicolaie
Genetic Lab, Bucharest, Romania.
M A
MA
Ionescu
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
G
G
Becheanu
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
F
F
Andrei
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
M
M
Diculescu
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
M
M
Ciocirlan
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D048750:Cell Nucleus Division; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics*; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D055815:Young Adult
D014408:Biomarkers, Tumor
biomarkers; colorectal cancer; cytokinesis; nuclear division index; screening