טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentLasry Valerie
SubjectA Novel Non-Invasive Approach for the Early Detection of
Colorectal Cancer: Quantifying Human DNA in Stool
from Fecal Occult Blood Test Cards
DepartmentDepartment of Biology
Supervisor Assistant Professor Ze'ev Lev
Full Thesis text - in Hebrew Full thesis text - Hebrew Version


Abstract

Colorectal cancer is a leading cause of morbidity and mortality in developed countries, including Israel. Early detection of this malignancy by periodic biennial as well as annual screening with the fecal occult blood test (FOBT) is the only non-invasive approach that has proven to be effective in reducing significantly the incidence and mortality rates of this disease. FOBT is a proven efficient way of reducing mortality and incidence of colorectal cancer. Yet, it has lower sensitivity and a relatively low positive predictive value. To improve the test efficacy, we suggested carrying out a biphasic, sequential approach employing the standard FOBT assay followed by genetic testing in DNA extracted from the same FOBT cards.

We have already shown that testing for K-ras mutations as a second test adds to the positive predictive value (PPV) of the FOBT test alone. However, the DNA mutation detection assay appears to be limited to a fraction of the tumors only and a more general marker is required. Much evidence support the idea that total human DNA quantity (HDQ) is elevated in the stool of colorectal cancer patients. To test HDQ as a marker that can be combined with FOBT for early detection of colorectal cancer, a total of 418 positive and 103 negative FOBT cards were processed. Human DNA was detected with the human-specific ALU probe. We found that the results are very promising. This is because the PPV for all tumors - 77% - was higher when the combined test was used compared with the FOBT assay alone.

The possibility of adding the new dimension of molecular markers to the current FOBT assay using the same card is exciting. We expect that the double-test, namely the fecal occult blood test combined with the molecular tests, will give better results than each test by itself, and will improve the efficiency of the early detection of colorectal cancer while still keeping it cost-effective.