Novel genetic and epigenetic alterations in ... - Ous-research.no

Introductionpopulation-wide screening program. The obstacles of this method are the cost andavailability of trained personnel, as well as reduced compliance over time. Randomized trailsdesigned to determine the efficacy with regards to incidence and mortality are thereforeneeded in order to justify the use of colonoscopy as a population based screeningprogram[123].The presence of occult blood in feces is considered an indication of CRC, and a fecal occultblood test (FOBT) is already in use as a screening program in several countries. FOBT isshown to reduce mortality by CRC with 15-33%, but the need for biannual testing hasresulted in a decrease in patient compliance over time and lower the effect of thescreening[123]. With different FOBT technologies, variable levels of sensitivity are obtained,ranging from 5%-99%, while specificity is somewhat higher 65%-99%[124;125]. Suchdiverse results indicate that the test is highly dependent on optimal sample preparation andanalysis. It also gives both a relatively high degree of false positive and false negativefindings. Positive predictive value, or precision rate, is the proportion of patients with whoare correctly diagnosed. It is the most important measure of a diagnostic method as itreflects the probability that a positive test reflects the underlying condition being tested for,and a high degree of false positives will make the precision rate decrease. On the contrary,negative predictive value is the proportion of patients with negative test results who arecorrectly diagnosed and in the same manner, a high rate of false negatives will impair thisnumber. A low precision rate results in unnecessary colonoscopies, hence reducing the costeffectiveness of FOBT screening. Also, FOBT will not detect benign precursor lesions[123].The requirement for better biomarkers is therefore needed from an early detection screeningperspective. A marker with both high sensitivity and specificity will not only prevent extracosts due to unnecessary colonoscopies, but may also increase the time-intervals betweenrepeated tests. Finally, optimal biomarkers should also be present in benign precursor stagesand thereby increase the time-window in which removing the polyp is considered curative.Prognostic and predictive markersSurvival is as mentioned associated with tumor phenotype, as patients with MSI tumorsgenerally have improved prognosis compared to patients with MSS tumors[59]. In addition,5-flurouracil (5-FU) based chemotherapy does not seem to provide survival benefits among34