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Screening for colorectal cancer: established and emerging modalities

Abstract

It has been estimated that >95% of cases of colorectal cancer (CRC) would benefit from curative surgery if diagnosis was made at an early or premalignant polyp stage of disease. Over the past 10 years, most developed nation states have implemented mass population screening programs, which are typically targeted at the older (at-risk) age group (>50–60 years old). Conventional screening largely relies on periodic patient-centric investigation, particularly involving colonoscopy and flexible sigmoidoscopy, or else on the fecal occult blood test. These methods are compromised by either low cost-effectiveness or limited diagnostic accuracy. Advances in the development of diagnostic molecular markers for CRC have yielded an expanding list of potential new screening modalities based on investigations of patient stool (for colonocyte DNA mutations, epigenetic changes or microRNA expression) or blood specimens (for plasma DNA mutations, epigenetic changes, heteroplasmic mitochondrial DNA mutations, leukocyte transcriptome profile, plasma microRNA expression or protein and autoantibody expression). In this Review, we present a critical evaluation of the performance data and relative merits of these various new potential methods. None of these molecular diagnostic methods have yet been evaluated beyond the proof-of-principle and pilot-scale study stage and it could be some years before they replace existing methods for population screening in CRC.

Key Points

  • Approximately 1 million new cases of colorectal cancer are diagnosed each year

  • Population screening for detection of disease at an early stage has demonstrated a significant reduction in mortality

  • The fecal occult blood test is the most widely adopted screening method, but is compromised by poor reliability and patient compliance

  • Although flexible sigmoidoscopy is cost-effective, more definitive direct investigative procedures (such as colonoscopy) are prohibitively expensive for most national screening programs

  • An expanding list of potential new screening methods based on the detection of DNA, RNA or protein molecular markers in patient stool or blood specimens is currently being evaluated

  • The introduction of screening based on molecular markers is likely to be an incremental process; established screening modalities are likely to remain in widespread use for some years

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Figure 1
Figure 2: Schematic outline of serum or plasma protein expression profiling by MALDI-TOF mass spectrometry.

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N. Pawa and J. D. Norton contributed to the research, discussion, writing and editing of this manuscript. T. Arulampalam contributed to the discussion of content and editing.

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Correspondence to John D. Norton.

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Pawa, N., Arulampalam, T. & Norton, J. Screening for colorectal cancer: established and emerging modalities. Nat Rev Gastroenterol Hepatol 8, 711–722 (2011). https://doi.org/10.1038/nrgastro.2011.205

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