1932

Abstract

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies’ assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80–90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-103018-123125
2020-01-27
2024-12-09
Loading full text...

Full text loading...

/deliver/fulltext/med/71/1/annurev-med-103018-123125.html?itemId=/content/journals/10.1146/annurev-med-103018-123125&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Siegel RL, Miller KD, Jemal A 2019. Cancer statistics, 2019. CA Cancer J. Clin 69:7–34
    [Google Scholar]
  2. 2. 
    Nishihara R, Wu K, Lochhead P et al. 2013. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N. Engl. J. Med. 369:1095–105
    [Google Scholar]
  3. 3. 
    Zauber A, Winawer SJ, O'Brien MJ et al. 2012. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N. Engl. J. Med. 366:687–96
    [Google Scholar]
  4. 4. 
    Shaukat A, Mongin SJ, Geisser MS et al. 2013. Long-term mortality after screening for colorectal cancer. N. Engl. J. Med. 369:1106–14
    [Google Scholar]
  5. 5. 
    Rex DK, Boland CR, Dominitz JA et al. 2017. Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastroenterology 153:307–23
    [Google Scholar]
  6. 6. 
    Carethers JM. 2015. Screening for colorectal cancer in African Americans: determinants and rationale for an earlier age to commence screening. Digest. Dis. Sci. 60:711–21
    [Google Scholar]
  7. 7. 
    Ahlquist DA. 2015. Multi-target stool DNA test: a new high bar for noninvasive screening. Digest. Dis. Sci. 60:623–33
    [Google Scholar]
  8. 8. 
    Lin JS, Webber EM, Beil TL et al. 2012. Fecal DNA testing in screening for colorectal cancer in average-risk adults: comparative effectiveness review Executive summary no. 52. AHRQ Pub. No. 12-EHC022-1 Rockville, MD: Agency for Healthcare Research and Quality https://effectivehealthcare.ahrq.gov/sites/default/files/related_files/colorectal-cancer-screening_executive.pdf. Accessed June 1, 2019
    [Google Scholar]
  9. 9. 
    Carethers JM. 2014. DNA testing and molecular screening for colon cancer. Clin. Gastroenterol. Hepatol. 12:377–81
    [Google Scholar]
  10. 10. 
    Grady WM, Carethers JM. 2008. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 135:1079–99
    [Google Scholar]
  11. 11. 
    Carethers JM, Jung BH. 2015. Genetics and genetic biomarkers in sporadic colorectal cancer. Gastroenterology 149:1177–90
    [Google Scholar]
  12. 12. 
    Cancer Genome Atlas Network 2012. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–37
    [Google Scholar]
  13. 13. 
    Carethers JM. 2016. Hereditary, sporadic and metastatic colorectal cancers are commonly driven by specific spectrums of defective DNA mismatch repair components. Trans. Am. Clin. Climatol. Assoc. 127:81–97
    [Google Scholar]
  14. 14. 
    Carethers JM. 2017. Microsatellite instability pathway and EMAST in colorectal cancer. Curr. Colorectal Cancer Rep. 13:73–80
    [Google Scholar]
  15. 15. 
    Carethers JM, Fearon ER. 2015. Molecular subtyping of colorectal cancer: time to explore both intertumoral and intratumoral heterogeneity to evaluate patient outcome. Gastroenterology 148:10–13
    [Google Scholar]
  16. 16. 
    Koi M, Garcia M, Choi C et al. 2016. Microsatellite alterations with allelic loss on 9p24.2 signify less aggressive colorectal cancer metastasis. Gastroenterology 150:944–55
    [Google Scholar]
  17. 17. 
    Coppede F, Lopomo A, Spisni R, Migliore L 2014. Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer. World J. Gastroenterol. 20:943–56
    [Google Scholar]
  18. 18. 
    Carethers JM. 2015. Biomarker-directed targeted therapy in colorectal cancer. J. Digest. Cancer Rep. 3:5–10
    [Google Scholar]
  19. 19. 
    Klaassen CH, Jeunink MA, Prinsen CR et al. 2003. Quantification of human DNA in feces as a diagnostic test for the presence of colorectal cancer. Clin. Chem. 49:1185–87
    [Google Scholar]
  20. 20. 
    Anderson BW, Ahlquist DA. 2016. Molecular detection of gastrointestinal neoplasia. Gastroenterol. Clin. N. Am. 45:529–42
    [Google Scholar]
  21. 21. 
    Sidransky D, Tokino T, Hamilton SR et al. 1992. Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science 256:102–5
    [Google Scholar]
  22. 22. 
    Zou H, Taylor WR, Harrington JJ et al. 2009. High detection rates of colorectal neoplasia by stool DNA testing with a novel digital melt curve assay. Gastroenterology 136:459–70
    [Google Scholar]
  23. 23. 
    Ahlquist DA, Sargent DJ, Loprinzi CL et al. 2008. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann. Intern. Med. 149:441–50
    [Google Scholar]
  24. 24. 
    Shen L, Toyota M, Kondo Y et al. 2007. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc. Natl. Acad. Sci. USA 104:18654–59
    [Google Scholar]
  25. 25. 
    Imperiale TF, Ransohoff DF, Itzkowitz SH et al. 2004. Fecal DNA versus fecal occult blood for colorectal cancer screening in an average-risk population. N. Engl. J. Med. 35:2704–14
    [Google Scholar]
  26. 26. 
    Bailey JR, Aggarwal A, Imperiale TF 2016. Colorectal cancer screening: stool DNA and other noninvasive modalities. Gut Liver 10:204–11
    [Google Scholar]
  27. 27. 
    Exact Sciences Corp. Cologuard® physician brochure. Madison, WI: Exact Sciences Corp https://cdn2.hubspot.net/hub/377740/file-1412311339-pdf/Document__LBL-0260[1].pdf?t=1534449532931. Accessed June 1, 2019
  28. 28. 
    Imperiale TF, Ransohoff DF, Itzkowitz SH et al. 2014. Multitarget stool DNA testing for colorectal-cancer screening. N. Engl. J. Med. 370:1287–97
    [Google Scholar]
  29. 29. 
    Ahlquist DA, Zou H, Domanico M et al. 2012. Next generation stool DNA test accurately detects colorectal cancer and large adenomas. Gastroenterology 142:248–56
    [Google Scholar]
  30. 30. 
    Redwood DG, Asay ED, Blake ID et al. 2016. Stool DNA testing for screening detection of colorectal neoplasia in Alaska native people. Mayo Clin. Proc. 91:61–70
    [Google Scholar]
  31. 31. 
    Yang D, Hillman SL, Harris AM et al. 2014. Patient perceptions of a stool DNA testing for pan-digestive cancer screening: a survey questionnaire. World J. Gastroenterol. 20:4972–79
    [Google Scholar]
  32. 32. 
    Cooper GS, Markowitz SD, Chen Z et al. 2018. Evaluation of patients with an apparent false positive stool DNA test: the role of repeat stool testing. Digest. Dis. Sci. 63:1449–53
    [Google Scholar]
  33. 33. 
    Johnson DH, Kisiel JB, Burger KN et al. 2017. Multitarget stool DNA test: clinical performance and impact on yield and quality of colonoscopy for colorectal cancer screening. Gastrointest. Endosc. 85:657–65
    [Google Scholar]
  34. 34. 
    Brenner H, Chen H. 2017. Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population. Clin. Epidemiol. 9:377–84
    [Google Scholar]
  35. 35. 
    Zhai R-L, Xu F, Zhang P et al. 2016. The diagnostic performance of stool DNA testing for colorectal cancer. Medicine 95:e2129
    [Google Scholar]
  36. 36. 
    Levin TR, Corley DA, Jensen CD et al. 2017. Genetic biomarker prevalence is similar in fecal immunochemical test positive and negative colorectal cancer tissue. Digest. Dis. Sci. 62:678–88
    [Google Scholar]
  37. 37. 
    Heigh RI, Yab TC, Taylor WR et al. 2014. Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT). PLOS ONE 9:e85659
    [Google Scholar]
  38. 38. 
    Cooper GS, Markowitz SD, Chen Z et al. 2018. Performance of multitarget stool DNA testing in African American patients. Cancer 124:3876–80
    [Google Scholar]
  39. 39. 
    Berger BM, Schroy PC III, Dinh TA 2016. Screening for colorectal cancer using a multitarget stool DNA test: modeling the effect of the interest interval on clinical effectiveness. Clin. Colorectal Cancer 15:e65–74
    [Google Scholar]
  40. 40. 
    Zauber AG, Lansdorp-Vogelaar I, Wilschut J et al. 2007. Cost-effectiveness of DNA stool testing to screen for colorectal cancer Technology Assessment Report Rockville, MD: Agency for Healthcare Research and Quality https://www.ncbi.nlm.nih.gov/books/NBK285164/. Accessed June 1, 2019
    [Google Scholar]
  41. 41. 
    Landsdorp-Vogelaar I, Kuntz KM, Knudsen AB et al. 2010. Stool DNA testing to screen for colorectal cancer in the Medicare population: a cost-effectiveness analysis. Ann. Intern. Med. 153:368–77
    [Google Scholar]
  42. 42. 
    Ladabaum U, Mannalithana A. 2016. Comparative effectiveness and cost effectiveness of a multitarget stool DNA test to screen for colorectal neoplasia. Gastroenterology 151:427–39
    [Google Scholar]
  43. 43. 
    Barzi A, Lenz HJ, Quinn DI, Sadeghi S 2017. Comparative effectiveness of screening strategies for colorectal cancer. Cancer 123:1516–27
    [Google Scholar]
  44. 44. 
    Bibbins-Domingo K, Grossman DC, Curry SJ et al. 2016. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA 315:2564–75
    [Google Scholar]
  45. 45. 
    Knudsen AB, Zauber AG, Rutter CM et al. 2016. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the U.S. Preventive Services Task Force. JAMA 315:2595–609
    [Google Scholar]
  46. 46. 
    Suehiro Y, Zhang Y, Hashimoto S et al. 2018. Highly sensitive faecal DNA testing of TWIST1 methylation in combination with faecal immunochemical test for haemoglobin is a promising marker for detection of colorectal neoplasia. Ann. Clin. Biochem. 55:59–68
    [Google Scholar]
/content/journals/10.1146/annurev-med-103018-123125
Loading
/content/journals/10.1146/annurev-med-103018-123125
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error