The Roadmap of Colorectal Cancer Screening

SIMPLE SUMMARY: Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. Fecal occult blood test screening reduces incidence and mortality. However, the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of CRC screening globally and the most recent approaches aimed at improving accuracy and participation in CRC screening, while also considering the need for gender and age differentiation. New fecal tests and markers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel markers, such as circulating mRNA, micro-RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods or arrays and sequencing assays that identify candidate biomarkers in blood samples. ABSTRACT: Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.