title: Molecular markers for colorectal cancer screening.
abstract: Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Faecal occult blood testing and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma-carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA and micro-RNA have all been evaluated. The observation of tumour cell exfoliation into the mucocellular layer of the colonic epithelium and proven stability of DNA in a harsh stool environment make stool DNA a particularly promising marker. The development of a clinically useful stool DNA test has required numerous technical advances, including optimisation in DNA stabilisation, the development of assays with high analytical sensitivity, and the identification of specific and broadly informative molecular markers. A multitarget stool DNA test, which combines mutant and methylated DNA markers and a faecal immunochemical test, recently performed favourably in a large cross-sectional validation study and has been approved by the US Food and Drug Administration for the screening of asymptomatic, average-risk individuals. The ultimate way in which molecular marker screening assays will be used in clinical practice will require additional studies to determine optimal screening intervals, factors affecting compliance, management of false-positive results, and the use of these assays in high-risk populations, as well as other considerations.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Dickinson
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kisiel
authors.affiliation: Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Ahlquist
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000032:analysis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D009780:Occult Blood; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: COLONIC NEOPLASMS; COLORECTAL CANCER; COLORECTAL CANCER SCREENING; MOLECULAR BIOLOGY; MOLECULAR ONCOLOGY