The use of molecular markers in the diagnosis of colorectal cancer screening

Background: Colorectal cancer (CRC) is among the most prevalent cancers. Despite remarkable advances in detection and treatment of the illness, more than a third of patients diagnosed with CRC ultimately succumb to the neoplastic lesions, mostly due to metastases. Chromosomal instability, DNA mismatch repair defects, epigenetic silencing due to aberrant methylation of promoters, defects in base excision repair and activation of oncogenic pathways are the prerequisites for CRC development. Early detection of CRC is of paramount importance and the key to ultimately curing the vast majority of patients.

Methods: Additionally to testing for fecal occult blood, assays for the detection of CRC-specific mutations and aberrant promoter methylation of fecal DNA and of DNA isolated from blood have been established. Moreover, assays for profiling DNA, RNA and proteins in plasma to detect CRC in early stages have been the focus of intense research.

Results: The improved and newly developed assays described in this article show the potential for strongly improved sensitivity at high specificity. Comparison of various assays shows that the accuracy of the tests strongly depends on the experimental setup and the samples used (e.g. blood vs. stool DNA, early vs. late cancer stage).

Conclusion: The broad implementation of screens for CRC with high sensitivity and specificity, as developed in recent years, should strongly increase the early detection of neoplastic transformations and thereby, the survival rate of cancer patients.