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Review
. 2021 Mar 4;13(5):1101.
doi: 10.3390/cancers13051101.

The Roadmap of Colorectal Cancer Screening

Affiliations
Review

The Roadmap of Colorectal Cancer Screening

Enea Ferlizza et al. Cancers (Basel). .

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.

Keywords: colonoscopy; ctDNA; extracellular vesicles; fecal immunochemical test (FIT); flexible sigmoidoscopy; liquid biopsy; mRNA; microRNA; proteins.

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Conflict of interest statement

R.S. and M.L. have intellectual property rights on an international patent pending (WO2016/185451: method and kit for diagnosis of colorectal cancer; USA patent number 10900085; European patent office number EP3298165). R.S., L.R. and M.L. have intellectual property rights on an international patent pending (WO/2019/138303: new prognostic method). The remaining authors (E.F. and M.S.) declared no conflict of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
World and colorectal cancer in 2020. (a) Estimated age standardized incidence rate (100,000) for world countries; (b) Estimated age standardized mortality rate (100,000) for the world countries. Modified from Global Cancer Observatory (GBO) 2020, International Agency for Research on Cancer, World Health Organization [6].
Figure 2
Figure 2
Colorectal cancer in Europe in 2020. (a) Estimated age standardized incidence rate (100,000) for European countries; (b) Estimated age standardized mortality rate (100,000) for the European countries. Modified from Global Cancer Observatory 2020, International Agency for Research on Cancer, World Health Organization [6].
Figure 3
Figure 3
Routine and new tests used or proposed for colorectal cancer screening. Guaiac fecal occult blood test (gFOBT), fecal immunochemical test (FIT), double-contrast barium enema (DCBE), computed tomographic colonography (CTC), colon capsule endoscopy (CCE), colonoscopy (CS), flexible sigmoidoscopy (FS), fluorescent long DNA (FL-DNA), not available (NA), false positive (FP). 1 The reported percentages of sensitivity and specificity refer to colorectal cancer. 2 Refers only to distal colorectal cancer. 3 Refers to advanced neoplasia. 4 Refers to the average value among 8 cancer types.

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